Methods of using a self-adjusting stent assembly and  kits including same

ABSTRACT

A method of using a self-adjusting stent assembly includes estimating body lumen diameter(s) associated with a portion of a body lumen in which a stent assembly will be placed; determining, based on the estimated diameter(s), target expanded stent diameter(s) of the stent assembly which is to be placed in the portion of the body lumen; selecting the stent assembly for stenting the portion of the body lumen, wherein the stent assembly is configured to: expand from an initial to expanded diameters within a range of expanded diameters; wherein the range of expanded diameters is from about 9 mm to about 5.5 mm; and wherein the target expanded stent diameter(s) is/are within the range of expanded diameters; and apply a chronic radial force to a wall that forms the portion of the lumen, wherein the radial force is less than about 0.33 N/mm; and implanting the stent assembly in the portion of the body lumen.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of the filing date of, and priorityto, U.S. Application No. 62/747,800, filed Oct. 25, 2018 bearingAttorney Docket No. 46141.96PV01, the entire contents of which is herebyincorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to stent devices and methods and,specifically, to the use of a self-expanding one-size-fits-all stentassembly for any body lumen diameter within a range of body lumendiameters, kits containing such stent assembly, and instructions tostent with such a stent assembly.

BACKGROUND

Self-expanding stents generally have a tubular shape cut in a patternthat results in spring-like movement of the stent assembly in the radialdirection. The stents are placed in a vessel and the spring-likemovement acts as a scaffold to support lesions, thereby hopefullyrestoring an adequate lumen in a vessel. Currently these devices aredesigned to fit a specific vessel diameter, and the indication of use isusually within 1-2 mm of the nominal diameter of the designed stent tominimize or avoid damage to the vessel wall. However, the variances invessel diameters may be 5 mm or larger. Thus, the physician or othermedical practitioner is required to use various imaging techniques todetermine which size of stent assembly is required. Additionally, thestent assembly may need to be placed in a portion of a vessel that has avaried vessel diameter. In this instance, the physician must choose asize that corresponds to only one of the vessel diameters and place itin that diameter portion of the vessel, or use a tapered stent assemblyto span the portion of the vessel that has a varied vessel diameter.Often, the physician might incorrectly choose the stent size, whichresults in an oversizing of the stent or under sizing of the stent.Under sizing may result in shifting of the stent or failure to achievefull stent apposition, raising the risk of thrombosis or mobilizationover the stent edges. Oversizing may result in stressing the walls ofthe vessel and generating re-stenosis or perforation.

SUMMARY

One aspect of the disclosure details a method of using a stent assemblyadapted to stent a range of body lumen sizes, which includes: providingstenting instructions that include instructions to: estimate body lumendiameter(s) associated with a portion of a body lumen in which the stentassembly will be placed, determine, based on the estimated body lumendiameter(s), target expanded stent diameter(s) of the stent assembly,select the stent assembly for stenting the portion of the body lumenbased on the target expanded stent diameter(s), wherein the stentassembly is configured to expand from an initial diameter to one or moreexpanded diameters within a range of expanded diameters while applying aradial force of about 0.20 N/mm to about 0.33 N/mm, wherein the range ofexpanded diameters is from about 5.5 mm to about 9 mm, and wherein thetarget expanded stent diameter(s) is/are within the range of expandeddiameters, and implant the stent assembly in the portion of the bodylumen; and providing the selected stent assembly in association with thestenting instructions.

In one embodiment, the stent assembly is configured to expand to alldiameters within the range of expanded diameters. In another embodiment,the portion of the body lumen in which the stent assembly will be placedincludes a lesion; and wherein the estimated body lumen diameter(s)include: a first estimated body lumen diameter that is spaced in a firstdirection from the lesion, and a second estimated body lumen diameterthat is spaced in a second direction from the lesion, wherein the firstdirection is opposite the second direction. In another embodiment, theinstructions further include instructions to: when the portion of thebody lumen defines varying body lumen diameters, allow a first portionof the stent assembly to expand to a first expanded diameter that iswithin the range of expanded diameters and allow a second portion of thestent assembly to expand to a second expanded diameter that is withinthe range of expanded diameters. In a preferred embodiment, the firstexpanded diameter is different from the second expanded diameter. In yetanother embodiment, the stent assembly includes a knitted stent jacket,including an expansible mesh structure formed from fibers having adiameter between about 7 micrometers and about 40 micrometers, and anexpansible stent, operatively associated with the knitted stent jacket,wherein the expansible mesh structure includes a retracted state that isassociated with the initial diameter and a deployed state that isassociated with the one or more expanded diameters, wherein theexpansible mesh structure defines apertures having a minimum centerdimension greater than about 100 micrometers and no more than about 300micrometers before implantation and when the expansible mesh structureis in the deployed state, wherein the expansible mesh structure has athickness of greater than about 12.5 micrometers to no more than about100 micrometers.

In another aspect, the disclosure encompasses a method of stenting,which includes: estimating a base reference diameter(s) associated witha portion of a body lumen in which a stent assembly will be placed,determining, based on the estimated base reference diameter(s), targetexpanded stent diameter(s) of the stent assembly which is to be placedin the portion of the body lumen, selecting the stent assembly forstenting the portion of the body lumen, wherein the stent assembly isconfigured to: expand from an initial diameter to one or more expandeddiameters within a range of expanded diameters, wherein the range of theone or more expanded diameters is from about 5.5 mm to about 9 mm, andwherein the target expanded stent diameter(s) is/are within the range ofthe one or more expanded diameters, apply a chronic radial force to awall that forms the portion of the body lumen in which the stentassembly will be placed, wherein the chronic radial force is less thanabout 0.33 N/mm, and implanting the stent assembly in the portion of thebody lumen.

In one embodiment, the method includes implanting the stent assembly inthe portion of the body lumen includes allowing the stent assembly toexpand to an expanded diameter within the range of expanded diameterssuch that the stent assembly applies the chronic radial force to thewall that forms the portion of the body lumen in which the stentassembly will be placed, and wherein the chronic radial force is greaterthan about 0.20 N/mm. In one preferred embodiment, the stent assembly isa configured to expand to all diameters between about 5.5 mm and about 9mm. In another preferred embodiment, when the portion of the body lumendefines varying body lumen diameters, implanting the stent assembly inthe portion of the body lumen includes: allowing a first portion of thestent assembly to expand to a first expanded diameter that is within therange of the one or more expanded diameters such that the first portionof the stent assembly applies the chronic radial force to the wall thatforms the portion of the body lumen in which the stent assembly will beplaced, and allowing a second portion of the stent assembly to expand toa second expanded diameter that is within the range of the one or moreexpanded diameters such that the second portion of the stent assemblyapplies the chronic radial force to the wall that forms the portion ofthe body lumen in which the stent assembly will be placed, and whereinthe chronic radial force is greater than about 0.20 N/mm. In anotherpreferred embodiment, the first expanded diameter is different from thesecond expanded diameter. In another preferred embodiment, the methodincludes allowing the first portion of the stent assembly to expand tothe first expanded diameter and allowing the second portion of the stentassembly to expand to the second expanded diameter occurssimultaneously. In another embodiment, the stent assembly includes: aknitted stent jacket, including an expansible mesh structure formed fromfibers having a diameter of about 7 micrometers to about 40 micrometers,and an expansible stent, operatively associated with the knitted stentjacket, wherein the expansible mesh structure includes a retracted statethat is associated with the initial diameter and a deployed state thatis associated with the expanded diameter(s), wherein the expansible meshstructure defines apertures having a minimum center dimension of atleast about 100 micrometers to no more than about 300 micrometers beforeimplantation and when the expansible mesh structure is in the deployedstate, wherein the expansible mesh structure has a thickness of at leastabout 12.5 micrometers to no more than about 100 micrometers.

In another aspect, the disclosure encompasses a method of stenting aplurality of body lumens, which includes: positioning a first stentassembly in a retracted state within a first body lumen, expanding thefirst stent assembly to place the first stent assembly in a deployedstate within the first body lumen, wherein, when the first stentassembly is in the deployed state, the first stent assembly has a firstexpanded diameter and applies a first radial force to a first wall thatforms the first body lumen, positioning a second stent assembly in aretracted state within a second body lumen that is different from thefirst body lumen, and expanding the second stent assembly to place thesecond stent in a deployed state within the second body lumen, wherein,when the second stent assembly is in the deployed state, the secondstent assembly has a second expanded diameter and applies a secondradial force to a second wall that forms the second body lumen, whereinthe first and second stent assemblies are at least substantiallyidentical, and the second expanded diameter is greater than the firstexpanded diameter, wherein the second expanded diameter is between about220% to about 110% of the first expanded diameter, and wherein thesecond radial force is greater than about 50% of the first radial force.

In one embodiment, the method includes expanding the second stentassembly to place the second stent assembly in the deployed state withinthe second body lumen includes, when the second body lumen definesvarying body lumen diameters: expanding a first portion of the secondstent assembly to the second expanded diameter that is within a range ofexpanded diameters, and expanding a second portion of the second stentassembly to a third expanded diameter that is within the range ofexpanded diameters, and wherein the range of expanded diameters is fromabout 9 mm to about 5.5 mm. In another embodiment, each of the first andsecond stent assemblies includes: a knitted stent jacket, including anexpansible mesh structure formed from fibers having a diameter of about7 micrometers to about 40 micrometers, and an expansible stent,operatively associated with the knitted stent jacket: wherein theexpansible mesh structure transitions from the retracted state to thedeployed state, wherein the expansible mesh structure defines apertureshaving a minimum center dimension of at least about 100 micrometers tono more than about 300 micrometers before implantation and when theexpansible mesh structure is in the deployed state, wherein theexpansible mesh structure has a thickness of at least about 12.5micrometers to no more than about 100 micrometers.

In another aspect, the disclosure encompasses a kit including: a stentassembly including: a knitted stent jacket, including an expansible meshstructure formed from a single fiber having a diameter from about 7micrometers to about 40 micrometers, and an expansible stent,operatively associated with the knitted stent jacket: wherein theexpansible mesh structure includes a retracted state and a deployedstate, wherein the expansible mesh structure defines apertures having aminimum center dimension of at least about 160 micrometers in thedeployed state, and wherein the expansible mesh structure has athickness of at least about 12.5 micrometers to no more than about 100micrometers, and instructions for use setting forth a method forexpanding the stent assembly to any expanded diameter in a range fromabout 5.5 mm to about 9 mm while applying a chronic radial force ofabout 0.2 N/m to about 0.33 N/mm.

In one embodiment, the instructions include instructions to: estimatebody lumen diameter(s) associated with a portion of a body lumen inwhich the stent assembly will be placed, determine, based on theestimated body lumen diameter(s), target expanded stent diameter(s) ofthe stent assembly, select the stent assembly for stenting the portionof the body lumen based on the target expanded stent diameter(s),wherein the stent assembly is configured to expand from an initialdiameter to any expanded diameter within the range of expanded diameterswhile applying a radial force of about 0.20 N/mm to about 0.33 N/mm,wherein the target expanded stent diameter(s) is/are within the range ofexpanded diameters, and implant the stent assembly in the portion of thebody lumen. In another embodiment, the stent assembly is a configured toexpand to all diameters within the range of expanded diameters. In yetanother embodiment, the instructions further include instructions to:when the portion of the body lumen defines varying body lumen diameters,allow a first portion of the stent assembly to expand to a firstexpanded diameter that is within the range of expanded diameters andallow a second portion of the stent assembly to expand to a secondexpanded diameter that is within the range of expanded diameters. In yetanother embodiment, the first expanded diameter is different from thesecond expanded diameter.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the disclosure pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the disclosure, examplemethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

Example non-limiting embodiments of the disclosure are described in thefollowing description, read with reference to the figures attachedhereto. In the figures, identical and similar structures, elements orparts thereof that appear in more than one figure are generally labeledwith the same or similar references in the figures in which they appear.Dimensions of components and features shown in the figures are chosenprimarily for convenience and clarity of presentation and are notnecessarily to scale. The attached figures are:

FIG. 1 is a perspective view of an enhanced stent apparatus, in an open,non-crimped mode, in accordance with an example embodiment of thedisclosure;

FIG. 2 is a cross-sectional side view of an enhanced stent apparatus, inaccordance with an example embodiment of the disclosure;

FIG. 3 is an illustration of an enhanced stent apparatus in an open modein situ, in accordance with an example embodiment of the disclosure;

FIG. 4 is a perspective view of an enhanced stent apparatus, withmultiple helical coils in an open mode, in accordance with an exampleembodiment of the disclosure;

FIG. 5 is a perspective view of an enhanced stent apparatus, in acrimped, closed mode, in accordance with an example embodiment of thedisclosure;

FIG. 6A is a perspective view of a knitted porous structure enhancedstent apparatus in an open mode, in accordance with an exampleembodiment of the disclosure;

FIG. 6B is a detailed view of a knitted porous structure, in accordancewith an example embodiment of the disclosure;

FIG. 7 is a perspective view of a braided porous structure enhancedstent apparatus, in accordance with an example embodiment of thedisclosure;

FIG. 8 is a perspective view of an enhanced stent apparatus, providedwith longitudinal non-stretchable wires, and horizontal stretchableelastomers in accordance with an example embodiment of the disclosure;

FIG. 9 is a perspective view of an enhanced stent apparatus, whereinporous structure is longer than the support element, in accordance withan example embodiment of the disclosure;

FIG. 10 is a perspective view of an enhanced stent apparatus, whereinporous structure is significantly greater in diameter than a crimpedsupport element, and is folded on itself for insertion into a lumen, inaccordance with an example to embodiment of the disclosure;

FIG. 11 is a perspective view of a porous structure significantlygreater in diameter than an at least partially deflated balloon whereinthe porous structure is folded on itself for insertion into a lumen, inaccordance with an example embodiment of the disclosure;

FIG. 12 illustrates the use of a funnel to reduce the diameter of atleast a porous structure, in accordance with an example embodiment ofthe disclosure;

FIG. 13 illustrates using a stretchable rubber tube for manufacturing acompressed porous structure, in accordance with an example embodiment ofthe disclosure;

FIG. 14 is a graph showing fiber thickness vs. percentage of porousstructure surface area that is structure, in accordance with an exampleembodiment of the disclosure;

FIG. 15 is a detailed illustration of a threading method for securing aporous structure to a support element, in accordance with an exampleembodiment of the disclosure;

FIG. 16 is a detailed illustration of a knotting method for securing aporous structure to a support element, in accordance with an exampleembodiment of the disclosure;

FIG. 17 is a cross-section view of an enhanced stent apparatus showing aporous structure folding technique, in accordance with an exampleembodiment of the disclosure;

FIG. 18 is a schematic showing a method for manufacturing a porousstructure, in accordance with an example embodiment of the disclosure;

FIG. 19A is an illustration of a typical aneurism;

FIG. 19B is an illustration of a prior art technique for treating ananeurism;

FIG. 19C is an illustration of a technique for treating an aneurism, inaccordance with an example embodiment of the disclosure;

FIG. 20 is a graphic illustration of a reaction force of prior artstents through crimping and then deployment, in accordance with anexample embodiment of the disclosure;

FIG. 21 is a graphic illustration of a reaction force of the stentapparatus of FIG. 1 through crimping and then deployment, in accordancewith an example embodiment of the disclosure;

FIG. 22 is a table detailing reaction forces of the stent apparatus ofFIG. 1 through crimping and then deployment, in accordance with anexample embodiment of the disclosure

FIG. 23 is a flow chart illustrating a method of operating the apparatusof FIG. 1, in accordance with an example embodiment of the disclosure;

FIG. 24 is a cross-sectional view of a vessel, in accordance with anexample embodiment of the disclosure;

FIG. 25 is a cross-sectional view of the stent apparatus of FIG. 1 in aretracted state and extending within the vessel of FIG. 24, inaccordance with an example embodiment of the disclosure;

FIG. 26 is a cross-sectional view of the stent apparatus of FIG. 1 in adeployed stated and extending within the vessel of FIG. 24, inaccordance with an example embodiment of the disclosure;

FIG. 27 is a table detailing aggregated, de-identified patientinformation relating to an experimental test of one embodiment of thestent assembly of FIG. 1, in accordance with an example embodiment ofthe disclosure;

FIG. 28A is a cross-sectional view of a slip ring in a reduced profileconfiguration, in accordance with an example embodiment of thedisclosure;

FIG. 28B is a cross-sectional view of a slip ring in a deployedconfiguration, in accordance with an example embodiment of thedisclosure;

FIG. 29 is cross sectional view of a porous structure with anendothelium cell layer overgrowing it, in accordance with an exampleembodiment of the disclosure;

FIG. 30 is an illustration of a prior art situation in which a clump ofendothelial cells detaches from a stent strut;

FIGS. 31a-31d show deployment of a self-expanding stent, according toembodiments of the disclosure;

FIGS. 32-35 show in situ details of a typical stent jacket material inthe art, in situ; and

FIG. 36 shows a portion of the knitted stent jacket, according toembodiments of the disclosure;

FIG. 37 shows a plan view of the knitted stent jacket of FIG. 36,according to embodiments of the disclosure;

FIGS. 38-39 show details of the material including the knitted stentjacket of FIG. 36, according to embodiments of the disclosure; and

FIG. 40 shows in situ details of the material shown in FIG. 9, accordingto embodiments of the disclosure.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

Aspects of the present disclosure address shortcomings of the prior art,which are noted above, by providing a so-called one-size-fits-all stentassembly. The one-size-fits-all stent assembly is configured for use ina wide range of body lumen diameters regardless of whether the bodylumen is a straight body lumen (having a generally consistent diameter)or a varied diameter body lumen (having changes in the diameter), oreven a branched or bifurcated body lumen. As such, use of theone-size-fits-all stent assembly eliminates or reduces sizing errors andreduces the number of different sized stent assemblies required to beavailable on-hand at a patient treatment or prevention facility, e.g., ahospital.

The instant application is divided into a number of labeled sectionswhich generally include, in order, descriptions of apparatuses (e.g.porous structures, stents, etc.), materials and methods formanufacturing the apparatuses, the usage of pharmaceuticals with theapparatuses, and methods of using the apparatuses. It should beunderstood that the section headings are for clarity only and are notintended to limit the subject matter described therein. Furthermore,some of the subject matter described in a particular section may belongin more than one section and therefore, some of the material couldoverlap between sections.

INTRODUCTION

Aspects of the present disclosure successfully address shortcomings ofthe prior art by providing a stent assembly that is configured to expandto any diameter within a range of diameters to provide a chronic radialforce between about 0.33 N/mm and about 0.20 N/mm.

In accordance with some embodiments of the present disclosure, the stentassembly reduces risks and errors associated with choosing a specificstent assembly size.

In accordance with some embodiments of the present disclosure, the stentassembly reduces the amount of stent assemblies required to remainon-hand. This can advantageously permit smaller medical institutions tocarry the cost of having stent assemblies on hand that work for avariety of body lumen sizes, and more generally minimize the cost ofhaving a large inventory of different devices on hand for emergencies.

In accordance with some embodiments of the present disclosure, the stentassembly provides a known predefined radial force expectancy for alldiameters in the range.

In accordance with some embodiments of the present disclosure, the stentassembly provides better adaptation to varying diameters of a bodylumen, such as a vessel, over the length of the implantation mesh.

In accordance with some embodiments of the present disclosure, the stentassembly includes a fiber having a low diameter that allows eachendothelial cell to fully cover and overlap one or more fibers, therebyforming a layer of endothelial cells that adhere to tissue on eitherside of such fibers. The thus formed endothelial layer is substantiallystable with a substantially reduced tendency to break away and formemboli, which can provide improved patient outcomes.

In accordance with some embodiments of the present disclosure, the meshfiber includes material that encourages adherence of endothelial cells,thereby encouraging endothelial layer stability.

In accordance with some embodiments of the present disclosure, the meshis not secondarily processed, for example, with a chemical coating thatmay diminish endothelial adherence. Additionally, the absence ofchemical coatings serves to maintain low bulk fibers and fiberjunctions, where a first fiber passes over or under a secondfiber—another feature that contributes to endothelial layer stability.In such embodiments, it is possible to have one or more pharmaceuticalagents imbued within a fiber, or in another layer or portion of thestent assembly, to provide the benefit of such an agent while avoidingthe deficiencies of a chemical coating.

In accordance with some embodiments of the present disclosure, each meshfiber is spaced a distance from a neighboring fiber thereby minimizingthe risk of, or preventing, a single endothelial cell from adhering tomore than one fiber, thereby reducing the chance that endothelial cellswill break free of the stent, for example as a result of natural stentpulsation during blood flow.

In accordance with some embodiments of the present disclosure, the stentjacket optionally includes a mesh that is knitted. In accordance withsome embodiments of the present disclosure, the stent jacket mesh isoptionally formed from a single fiber or a single group of fibers.

Overview of Enhanced Stent Apparatus

The present disclosure, in some embodiments thereof, relates to stentassemblies, as presented in PCT Patent Application PCT/IB2006/051874,the disclosure of which is hereby incorporated herein by expressreference thereto. The methods and kits disclosed herein may, e.g., usevarious stent assemblies disclosed in that PCT application.

In an example embodiment of the disclosure, an apparatus is providedwhich includes a porous structure and, optionally, an underlying supportelement, such as a stent (wherein underlying means the porous structureis between the support element and a lumen wall).

In some example embodiments of the disclosure, an enhanced stentapparatus, including the porous structure and a stent, is used to treatstenosis and/or restenosis. In some example embodiments of thedisclosure, the enhanced stent apparatus furnishes at least one of amultiplicity of benefits over a conventional arterial stent. Forexample, the enhanced stent apparatus is optionally used to preventplaque from getting into the blood stream to cause embolism, since theporous structure is made with small enough apertures (sizes indicatedbelow) to hold detached plaque in place. In an embodiment of thedisclosure, use of a porous structure replaces the use of an embolismprotection device during stent implantation. Optionally, the “umbrella”type embolism protection device is not used. Optionally, the porousstructure is used in conjunction with an embolism protection device forenhanced protection over the method of using an embolism protectiondevice during the implantation of a conventional arterial stent. In anembodiment of the disclosure, the enhanced stent apparatus delivers morecomprehensive pharmacological assistance to a treated area thanconventional stents. In some embodiments of the disclosure, the enhancedstent apparatus is optimized to encourage endothelial cell growth and/ormigration. For clarity, the porous structure may be the mesh stentjacket described herein.

FIG. 1 shows a perspective view of an enhanced stent assembly or stentapparatus 100, in an example embodiment of the disclosure. A supportelement 102 is designed and constructed to expand a blood vessel in aradial fashion from a central axis 106 of the enhanced stent apparatus100. Optionally, support element 102 is tubular in shape. In someexample embodiments of the disclosure, support element 102 isconstructed of a flexible, biocompatible material. Optionally, supportelement 102 is constructed of stainless steel, nitinol, and/or cobaltchromium and/or other metal alloys (e.g. magnesium alloy). Optionally,support element 102 is constructed of polymer either biostable orbioresorbable. In some example embodiments of the disclosure, supportelement 102 is a vascular stent, such as those made by Cordis®, BostonScientific® and/or Medtronic®, for example.

In an example embodiment of the disclosure, support element 102 iscovered by at least one porous structure 104. Optionally, supportelement 102 acts as a support structure for porous structure 104, forexample to provide radial support and or to maintain a desired shape ofporous structure 104. FIG. 2, shows a cross-sectional view of anenhanced stent apparatus. In this embodiment, support element 102supplies structural support to porous structure 104, which is located onthe exterior of support element 102.

In some example embodiments of the disclosure, porous structure 104 islaid on the exterior of support element 102 and thereby overlaps gaps insupport element 102 (making the aperture sizes of the device as a wholesmaller, for example 150 microns), since conventional stent constructionusually results in multiple gaps in the structure of the stem, typicallyseveral millimeters. In other example embodiments of the disclosure,porous structure 104 covers only a portion of support element 102. Forexample, only a portion of support element 102 is covered to avoidrestricting luminal flow to a branching vessel.

In some example embodiments of the disclosure, porous structure 104extends past at least one end of support element 102. This can, forexample, better treat the inside surface of a blood vessel at an edge ofenhanced stent apparatus 100, where it is more likely to haverestenosis. In an example embodiment of the disclosure, porous structure104 pads and/or treats trauma caused by the edge of support element 102by extending past at least one end of support element 102. Optionally,porous structure 104 extends no more than 1 mm past the end of supportelement 102. Optionally, porous structure 104 extends over 1 mm past theend of support element 102. Optionally, porous structure 104 extendspast only one end or both ends (as shown in FIG. 9) of support element102.

In some example embodiments of the disclosure, porous structure 104 isattached to support element 102 to prevent porous structure 104 fromunraveling and/or causing tissue irritation and/or avoiding dislodgmentof the porous structure from the support element during deployment.Optionally, the end of porous structure 104 is folded over the end ofsupport element 102 and attached, providing padding to a potentiallytrauma causing edge. Optionally, the end of porous structure 104 isfolded under itself and is held folded due to the pressure between thesupport element and the lumen. In an embodiment of the disclosure, atreatment, such as heat, is used to make the fold sharp and/orpermanent.

It should be understood that while an example configuration of enhancedstent apparatus is shown in FIGS. 1 and 2, other configurations couldpossibly be used, including: a porous structure 104 over apharmaceutical eluting support element; a pharmaceutical eluting porousstructure over a support element 102; a pharmaceutical to eluting porousstructure over a pharmaceutical eluting support element; a supportelement in between at least two porous structures, optionally some orall eluting pharmaceuticals; and, an enhanced stent including aplurality of layers which exhibit different optional characteristicssuch as degradation time and/or pharmaceutical elution. It should beunderstood that any of the above configurations include biodegradableand/or bioresorbable materials. Optionally, configurations are chosenfor specific treatment regimens indicated by the condition of thepatient.

In some example embodiments of the disclosure, porous structure 104 isused to control the local pressure exerted by the enhanced stentapparatus on the body lumen wall. For example, by increasing ordecreasing the coverage area of the porous structure as it at leastpartially covers the stent, the pressure exerted by the enhanced stentapparatus per unit area can be altered. In some embodiments of thedisclosure, modification of the coverage area considers factors such asthe stiffness of support element 102 and the geometry and/or coveragearea of the support struts of support element 102. In an embodiment ofthe disclosure, pressure control is used to reduce the likelihood of theenhanced stent apparatus causing plaque to break off of the lumen wall.In some embodiments of the disclosure, pressure control is used toreduce tissue trauma typically caused by stent implants, therebyenhancing protection against stenosis/restenosis. Furthermore, in someembodiments of the disclosure, support element 102 struts which couldnot be used previously due to the likelihood of trauma to the lumentissue can optionally be used in combination with porous structure 104.

In some example embodiments of the disclosure, bile ducts are treatedusing at least a porous structure as described herein. For example, thebile ducts often become congested with debris (e.g. cholesterol) whichrestricts flow. Treatment of the bile ducts using enhanced stentapparatus may increase the diameter of the bile ducts, improving theiroperation.

It is known that varying types of body lumens possess varying surfacetextures, both varying from each other, and sometimes within one type oflumen. Thus, in some example embodiments of the disclosure, differentporous structures with varying surface texture configurations aremanufactured and/or used depending on the interior surface texture of alumen being treated. For example, peaks and valleys in a body lumen arefitted with counter peaks and valleys of a porous structure (i.e. porousstructure counter peak goes into lumen valley and porous structurecounter valley accepts lumen peak). Optionally, the counter peaks andvalleys are of the same magnitude as the peaks and valleys found in thelumen being treated.

It should be understood that the aperture size, the porous structurethickness, the fiber thickness (or French), and/or the coverage area arevaried for different applications. For example, when treating thecarotids, debris of more than 100 microns should be prevented fromreaching the brain, thus the porous structure is designed such that whenstent is expanded, usually to about 8 millimeters, the majority ofaperture sizes are less than 100 microns. As another example, whentreating the coronaries larger debris (>100 microns) is not asproblematic, while the endotheliazation process and the non-restrictionof flow to side branches is more important. Thus, for coronary arteryapplications, when the support element 102 is in an expanded position,usually about 3 millimeters in diameter, the apertures in the porousstructure are optionally larger than 100 microns and below 300 microns.In some embodiments of the disclosure, the rate of endothelium cellgrowth over porous structure may be modified by increasing and/ordecreasing fiber thickness and porous structure thickness.

In an example embodiment of the disclosure, porous structure 104 isunder 100 microns in thickness. In some example embodiments of thedisclosure, the porous structure is less than 30 microns thick.Optionally, the porous structure is less than 10 microns in thickness.For example, the porous structure is less than 5 microns or 1 micronthick. Porous structure 104 optionally includes at least one fine,thread-like fiber. In some example embodiments of the disclosure, porousstructure 104 includes at least one fiber that is 40 nm to 40 micronsthick. Optionally, to the fiber thickness is similar to or less than thediameter of an endothelial cell to encourage endothelial cell growthbetween fibers and/or around at least one fiber. In an exampleembodiment of the disclosure, a super-fiber is used to construct porousstructure 104, wherein the super-fiber is made of multiple fibersbraided together. Optionally, super-fibers are used to enhance thestrength of porous structure 104.

In an example embodiment of the disclosure, the fibers of porousstructure 104 are spun and/or knitted and/or woven and/or braided toprovide structure to and apertures 110 in porous structure 104.Optionally, the porous structure is woven in an even pattern.Optionally, the porous structure is constructed so that the fibers arerandomly positioned in porous structure 104. Optionally, polymer fibersare used to construct porous structure 104. Optionally, polymercoverings are applied to porous structure 104 and/or support element102. Example porous structure manufacture is described in more detail inthe “Methods of Manufacture” section below.

In an example embodiment of the disclosure, the polymer covered porousstructure 104 is optionally made out of a closed interlocked designand/or an open interlocked design, or semi open design, similar totypical support element 102 designs. The open interlocked design has anadvantage when side branching is needed. When treating a junction of twoblood vessels, there is sometimes a need to introduce one stent throughthe side of another one. An open interlocked design allows such aprocedure, and when the porous structure is made of metal mesh, an openinterlocked design is utilized in order to allow easy side branchingstents. Optionally, using a biodegradable polymer coating on anon-biodegradable support element 102 leaves the support element 102embedded after the biodegradable polymer has degraded.

In an example embodiment of the disclosure, porous structure 104 iscrimped to a small diameter while still maintaining its flexibility, toenable successful maneuverability through a patient's blood vessels tothe site where enhanced stent apparatus 100 is to be implanted. In anexample embodiment of the disclosure, porous structure 104 is expandableto enable expansion of porous structure 104 with support element 102upon deployment at a treatment site within a patient's blood vessel.Optionally, expansion of porous structure 104 along the longitudinalaxis matches the expansion of support element 102 along the longitudinalaxis.

In an example embodiment of the disclosure, at least porous structure104 is expandable without significant foreshortening or elongation ofthe length of porous structure 104. For example, and in someembodiments, at least the porous structure 104 is expandable with lessthan about 20% foreshortening, with less than about 15% foreshortening,with less than about 10% foreshortening, or with less than about, orabout, 6% foreshortening. Generally, a percent of foreshortening isdefined as 100×(change in length÷loaded or final length). Optionally,porous structure 104 expands differently than support element 102, forexample using sliding connections described herein. As describedelsewhere herein, in a knitted embodiment of porous structure 104,expansion occurs at least partially as a result of the knittedstructure, and not necessarily because of the elasticity of the fiberused in constructing porous structure 104. In an embodiment of thedisclosure, at least one fiber which includes porous structure 104 isprovided with slack during manufacture to provide additional fibermaterial when porous structure 104 expands. FIG. 8 shows a perspectiveview of an enhanced stent apparatus 900. Enhanced stent apparatus 900 isprovided with non-stretchable wires 902, and stretchable elastomerfibers 904, in accordance with an example embodiment of the disclosure.Such an embodiment assists with the preservation of overall apparatus900 length while allowing expandability and flexibility duringimplantation.

In an example embodiment of the disclosure, an enhanced stent apparatusis provided which includes at least an expandable support element and anexpandable porous structure. The support element is optionally a stent,examples of which are known in the art for providing treatment to a widerange of body lumens. In an embodiment of the disclosure, the porousstructure has structure which resembles to fishing net. In an embodimentof the disclosure, the porous structure is knitted from a fiberapproximately 15-20 microns in diameter, has a coverage area of lessthan 20%, and which has aperture sizes approximately 150×200 microns. Insome embodiments of the disclosure, the porous structure is at leasttemporarily attached to support struts of the support element bystitching. Optionally, the stitches are loose, allowing the porousstructure to slide on the support struts, for example to provide extraexpandability as described herein with respect to FIG. 15. In someembodiments of the disclosure, the stitching is biodegradable. In someembodiments of the disclosure, the support element and/or the porousstructure are adapted to elute pharmaceutical agents into the body lumenbeing treated.

In some embodiments of the disclosure, different characteristics of theenhanced stem apparatus are chosen based on the intended use ortreatment to be rendered. For example, aperture sizes are optionallychosen based on a desire to provide embolic shower protection againstdebris of a certain size. As another example, coverage area isoptionally selected for modifying local pressure on the lumen beingtreated. Many of these characteristics are interrelated, as describedherein and shown in FIG. 14, for example.

In an embodiment of the disclosure, porous structure 104 is flexible toallow the lumen to naturally change its diameter, to account forpressure changes in the lumen and/or to respond to muscular activity. Insome embodiments of the disclosure, the porous structure 104 dividedinto a plurality of semi-independent sectors, which react differently tostimuli within or from the lumen. Optionally, the sectors are used toprevent banding of the lumen across the entire length of the porousstructure 104.

Example Characteristics and Performance of Porous Structure

Manufacturing techniques, described in more detail below, such asknitting which provide slack to individual fibers, or sections, ofporous structure 104, enable porous structure 104 to optionally expandupon deployment up to 10 times its diameter at insertion (insertiondiameter is described in more detail below), in an embodiment of thedisclosure. For example, in coronary applications porous structure 104may expand from 1 mm to 3 mm in diameter. In other examples, porousstructure 104 may expand from 2 mm to 8 mm in carotid applications,while in brain applications porous structure 104 may expand from 0.3 mmto 2.5 mm. These numbers are approximate and are by way of example only.In an embodiment of the disclosure, expansion of porous structure 104 iseffectuated in at least one of three ways: 1) the knitted/braided/wovenstructure of porous structure 104 (including slack in the fibers andcurly fibers); 2) the fiber from which the porous structure 104 is madeis at least slightly elastic; 3) sliding connections (described below)between porous structure 104 and support element 102 permit shifting ofporous structure 104 during expansion with respect to support element102, within certain limits. In an embodiment of the disclosure, thefiber from which porous structure 104 includes from about 2% to about80% of non-elastic materials. In some embodiments of the disclosure, theelastic material of the fiber from which porous structure 104 is madeallows for expansion up to 1000% its original size.

In some example embodiments of the disclosure, porous structure 104exhibits a high durability when subjected to twisting, turning,compression and/or elongation, which allows porous structure 104 towithstand the delivery process through the patient's vasculature to atreatment site. In an embodiment of the disclosure, porous structure 104can be loosely attached to a support element 102 at several locationsand folded for insertion into a lumen. The folded porous structure 104provides a reduced diameter apparatus for easier insertion into bodylumen(s) of the patient.

In some example embodiments of the disclosure, 20% of the total area ofporous structure 104 includes apertures having an approximate diameterno greater than 50, 200 or more than 200 microns in an expandedconfiguration. It is recognized that during the course of manufacturingthe porous structure, for example with certain manufacturing techniqueslike electrospinning and/or knitting, apertures created within theporous structure may overlap. This overlap effectively creates anaperture size which is smaller than specified. However, in some exampleembodiments of the disclosure, the effective, nominal aperture size isno greater than 50, 200 or more than 200 microns in diameter. In someembodiments of the disclosure, aperture sizes are selected to encourageendothelial cell overgrowth at a certain rate.

It should be noted that shapes of apertures are likely to vary at leastsomewhat as a result of manufacture and/or desired properties of porousstructure 104. For example, in a knitted porous structure, apertures aremost likely to be roughly square. In contrast, use of a weavingtechnique to manufacture porous structure likely produce square and/orrectangular shaped apertures whereas a braided porous structure islikely to exhibit quadrilateral shaped apertures, such as in FIG. 7. Indescribing an approximate “diameter” of an aperture, it should berecognized that all, some or none of the apertures will be actualcircles, squares, rectangles and/or quadrilaterals capable of simplisticarea measurement using diameter. Therefore, description using diameteris merely an approximation to convey example aperture sizes. Forexample, “diameter” could be the distance between two parallel sides ofa quadrilateral, such as a square or rectangle.

In some parts of the following description, aperture sizes describedherein are in reference to their size upon porous structure deploymentin a lumen. In other parts, the sizes refer to the aperture sizes whencrimped. Sometimes, the aperture sizes described herein refer to theirsize in a state intermediate a crimped and deployed configuration. Incontext, it should be easily perceived which of the above configurationsapplies, however, in the event it is not clear the aperture sizes couldbe considered as applying to expanded, crimped or intermediateconfigurations. When a fiber diameter is referred to, it relates to thefiber used to construct the porous structure 104. For example, if porousstructure 104 is constructed from a super-fiber including a bundle of 10fibers each 2 microns in diameter, the overall super-fiber diameter isabout 20 microns. Furthermore, it should be understood that referencesto fiber diameter are for approximation and convenience only and doesnot imply that the fiber is necessarily round. Optionally, fiber sizesare measured in French sizes, for example 0.003 Fr.

Referring to FIG. 14, a graph 1500 is shown which correlates fiberthickness of porous structure with percentage of the coverage area of asupport element, for a porous structure with a fishing net typeconfiguration. It can be seen that the general trend is that as thefiber sizes get thinner, the amount of porous structure surface areadedicated to structure is reduced. In an embodiment of the disclosure,it is desirable to have under 25% coverage area. Optionally, porousstructure 104 exhibits less than 20% coverage area. In an embodiment ofthe disclosure, the coverage area of the porous structure is adapted tobe minimized while still performing an intended lumen treating function,such as those described herein. In some embodiments of the disclosure,the coverage area of porous structure 104 is minimized in order to avoidundesirable clinical side effects. For example, lumen tissue irritationand pyrogenic effects are considerations for minimizing the coveragearea and optionally other characteristics such as aperture size, porousstructure thickness and/or fiber thickness, of porous structure 104.

In some example embodiments of the disclosure, the proportion ofstructure to apertures of porous structure 104, fiber size and/orapertures are sized in order to allow easy diffusion through porousstructure 104 and to facilitate growth of endothelial cells. Since thefiber 2202 diameters used in construction of porous structure 104 are onthe order of the size of the endothelial cells 2204, or smaller, asshown in FIG. 29, the integrity of the cells grown over the porousstructure will be much better than what is achieved in the prior art. Anindividual cell, statistically, will have a firm connection to the bloodvessel wall, since it is of the same order or larger than the fiberdiameter, thus anchoring itself, in an embodiment of the disclosure, inmore than one location to its native basalamina intimal layer andenabling better growth conditions. It is thus expected that the chanceof late or sub-acute thrombosis can be reduced over what is currentlyachieved when treatment is performed using a pharmaceutical elutingstent. In addition, porous structure 104 effectively acts as an embolicshower protection device, holding detached plaque in place, preventingit from traveling from the vessel wall into the blood stream. It shouldbe noted that porous structure 104 is configured, accounting for fiberthickness, porous structure thickness and/or aperture size such thatendothelial cells will overgrow porous structure 104, and optionallysupport element 102, in order to secure the enhanced stent in placeand/or insulate the foreign material of support element 102 and/orporous structure 104 from the bloodstream. In an example embodiment ofthe disclosure, endothelial cell layer overgrowth of porous structure104 is established within hours of implantation. In an embodiment of thedisclosure, overgrowth is accomplished within this time frame due tocharacteristics of porous structure 104 as they relate to endothelialcells, for example, the overall thickness being on the same order of, orsmaller, than an individual endothelial cell. In some embodiments of thedisclosure, it is conceived that a patient's average stay in thehospital after a stenting procedure can be reduced as a result of thespeed of endotheliazation using enhanced stent apparatus. In addition,the speed and efficacy of pharmaceutical treatment can expected to beenhanced as a result of the rapid endotheliazation over at least porousstructure 104 of enhanced stent apparatus 100.

FIG. 30 shows a disadvantage of using prior art drug eluting stentswherein a clump of endothelium cells has become detached from the stentstrut 2304, revealing an exposed “island” 2302 of the stent. Sometimes aclump falls off strut 2304 due to poor adhesion of the endothelium cellsto the polymer coating of the strut 2304. Contributing to this pooradhesion, the stent strut 2304 is typically an order of magnitude largerthan a single endothelium cell, thereby necessitating the creation of alarge endothelium cell bridge to cross the strut. The exposed island2302 can serve as a seed for thrombosis development. In some embodimentsof the disclosure, porous structure 104 is constructed to reduce thelikelihood of endothelial cells falling from the porous structure,thereby reducing the chance of development of late or sub-acutethrombosis and exposure of support element 102 to substances within thelumen. For example, endothelial cell retention is optionally encouragedby constructing porous structure 104 from at least one fiber of athickness and with aperture sizes (to permit growth of endothelial celltherethrough), such as described herein. Optionally, endothelial cellsare encouraged to remain on the porous structure by using a fiber layerof a thickness such as those described herein. Optionally, the linearnature of a single fiber porous structure 104, such as shown in FIG. 29,reduces the possibility of a large clump of endothelial cells becomingdislodged. In an embodiment of the disclosure, porous structure 104,optionally imbued with a pharmaceutical, is placed on the interior of abare metal or drug eluting support element in order to reduce thethrombogenicity of the support element. For example, by encouragingendothelial cell growth thereover and/or by reducing the exposed surfacearea of the support element by covering a portion of it up.

As suggested above, using a thin fiber whose thickness is similar to, orsmaller than, the diameter of an endothelial cell enables an endothelialcell layer to grow over porous structure 104 while still being closelytied to the basal intima layer at least at two points of the endothelialcell, one point on each side of porous structure 104. In an embodimentof the disclosure, the anchoring effect of this basal intima layer onthe endothelial cell layer reduces the chance of parts of theendothelial cell layer breaking off and entering the lumen. This, ineffect, reduces the chances of embolism in the patient and/or alsoreduces the likelihood of foreign bodies (e.g. the stent and the porousstructure) coming into contact and reacting with the contents of thelumen being treated. In the event that a clump of several endotheliumcells falls from porous structure 104, exposing a piece of the fiber, itis believed that there is a reduced chance of harm to the patient sincethe linear, single endothelial cell width geometry is not asthrombogenic as that shown in FIG. 30, where a clump of endothelialcells at least several cells in diameter has fallen off. In addition,the re-endotheliazation will be faster on an exposed porous structure104 than on the exposed strut 2304 for at least the reason that in thecase of the porous structure 104, an endothelial cell layer is formedwhen just one endothelial cell overgrows the endothelial cell sizedfiber used to construct the porous structure. In contrast, endothelialcell layer overgrowth is only accomplished after multiple endothelialcells have covered the exposed island.

In an embodiment of the disclosure, the reduced risk of late orsub-acute thrombosis by using porous structure 104 for pharmaceuticalelution optionally allows for a duration and/or dosage reduction in theuse of anti-coagulants by the patient.

In some example embodiments of the disclosure, fiber thickness, porousstructure thickness and/or aperture size are all separately varieddepending on the application of porous structure 104 and the needs ofthe patient. For example, in the coronary arteries it is sometimeshelpful to provide for good pharmaceutical dispersion. In such anexample, fibers including porous structure 104 are optionally locatedcloser together in order to allow for more complete transmission of apharmaceutical to patient.

In some example embodiments, when large molecule drugs, which have apoor diffusion into the tissue, are used to fight restenosis, the porousstructure can be soaked and/or imbued with an appropriate drug in orderto better diffuse it. The maximum concentrations of most of the drugsused are rather limited due to side effects and over toxicity, and atthe same time the concentration is not enough in order to allow theoptimum pharmacokinetics in areas not covered by the stent struts. Theporous structure mesh, having a better geometrical cover of the stentarea, provides a better and more optimum pharmacokinetics to the wholearea covered by the stent. For example, when high Dalton-large moleculedrugs are used, or when liposomes are the carriers of the treatmentagents, or when the stereo-chemical structure of the drug is largeand/or complicated, and/or when the drug is hydrophobic, relatively evendistribution of the drug is highly desirable. In some exampleembodiments of the disclosure, pharmacokinetics is also optimizedbecause the drug is located on/in the fibers of porous structure 104,and is covered and sealed within an endothelium layer, which helps thedrug from being washed away by the blood.

In some example embodiments of the disclosure, such as in a bypass veingraft, side branching is not an issue, therefore aperture sizes areoptionally made smaller, but not so small as to prevent endothelial cellgrowth therethrough. In another example embodiment of the disclosure,such as in the carotid arteries, side branching is not generallyconsidered a problem, but catching debris is. Therefore, in some exampleembodiments of the disclosure, the aperture sizes of porous structure104 are decreased to as little as 20 microns in diameter. In otherapplications, the aperture size can be increased to 50, 100, 200 or evenmore then 200 microns, depending on the application of enhanced stentapparatus 100.

In some example embodiments of the disclosure, a plurality of porousstructures is used. Optionally, at least one porous structure is locatedon the interior of support element 102, inside the lumen of supportelement 102. Optionally, more than one porous structure is located onthe exterior surface of support element 102. In some example embodimentsof the disclosure, at least some of the porous structures located onsupport element 102 are configured to be “in-phase” where the aperturesof the porous structures coincide with one another. Optionally, theporous structures are “out-of-phase” where the apertures are configuredto not coincide with one another. In an example embodiment of thedisclosure, an “out-of-phase” configuration is used to improve contactsurface area between porous structures and the lumen interior surface.In an embodiment of the disclosure, increased contact surface area canimprove pharmacokinetics, reduce local pressure exerted by porousstructure 104 on the lumen wall, improve embolic shower protectionand/or realize other advantageous effects. In some example embodimentsof the disclosure, porous structure 104 is constructed in the same shapeand pattern as support element 102, but on a smaller scale.

Example Materials of Manufacture

It should be noted that in some example embodiments of the disclosure, astretchable and/or expandable porous structure 104 is desired.Therefore, in some embodiments of the disclosure, materials are chosenwhich are either a) stretchable and/or b) can be used to manufacture aporous structure which is stretchable (e.g. a knitted structure). Insome example embodiments of the disclosure, biodegradable (i.e. arebroken down by the body) and/or bioresorbable (i.e. are absorbed intothe body) materials are used. In addition, blends of materials are usedin accordance with some embodiments of the disclosure. In an embodimentof the disclosure, a material is chosen because it exhibits durabilityduring manufacture, deployment and/or use despite being thin. In anembodiment of the disclosure, other considerations for the material tobe used are their biocompatibility, toxicity, hemocompatibility, andthrombogenicity.

Example materials for manufacturing porous structure 104 includenatural-based materials such as modified cellulose and/or collagen. Insome embodiments of the disclosure, metal fibers are used to constructporous structure, optionally constructed of stainless steel, and/or CoCrand/or CoNi alloy among other possibilities. Optionally, the metalfibers used are coated with at least one polymer. In some embodiments ofthe disclosure, porous structure is manufactured from a shape memoryalloy, such as nitinol. Optionally, carbon fiber is added to porousstructure 104 in order to improve strength characteristics of porousstructure 104. Optionally, glass fiber is added to porous structure 104in order to improve strength characteristics of porous structure 104.Optionally, a durable, resorbable and/or degradable fiber is added toporous structure 104 in order to improve strength and durabilitycharacteristics of the fiber during manufacture, which is degraded orresorbed or washed away to leave a thinner porous structure 104.

In an embodiment of the disclosure, some polymer fibers are chosen foruse in constructing porous structure 104 because they are elastic,biocompatible, hemocompatible, can be made not to stick to endotheliumtissue, are selectably bio-stable and/or biodegradable, exhibit therequisite mechanical strength, are sterilizable, have a high temperaturetransformation zone (solid and non-sticky at 37° C.), are capable ofhosting an effective amount of pharmaceuticals, and/or can releaseembedded pharmaceuticals at a controlled rate. In some exampleembodiments of the disclosure, other materials which exhibit some or allof these properties are optionally used to construct porous structure104. Optionally, coatings are put on porous structure 104, includingmaterials which exhibit some or all of these properties.

Polymer fibers are optionally made out of any of the followingmaterials: thermoplastic polymers for example polyethylene terephthalate(PET), polyolefin, oxidized acrylic, PTFE, polyethylene co-vinylacetate, polyethylene elastomer, PEO-PBT, PEO-PLA, PBMA, polyurethane,Carbosil (PTG product), medical grade polycarbonate urethanes, Nylon,PEEK-Optima, carboxylic acid moiety including one or more of a polyacrylic acid, a poly methacrylic acid, a maleic acid, a helonic acid, ataconic acid and/or combinations and/or esters of these monomers,thermoplastic polymers, thermosetic polymers, polyolefin elastomers,polyesters, polyurethanes, polyfluoropolymers, and/or nylon. Optionally,the fibers are constructed of an elastomer. Optionally, the fibers areconstructed of a coated fiber with a drug and polymer coating mixed toget a predetermined drug release characteristic, either coating over ametal and/or over a polymer fiber. Optionally, the fibers areconstructed of other materials than the example materials listed above.Example polymers which are optionally used for this purpose aremanufactured by Cordis®, Surmodix®, BostonScientific®, Abbott® andHemoteq® Polymers. Optionally, these polymers are selected for at leastone of the reasons specified in the paragraph above. Optionally, thecoating is used to facilitate the elution of pharmaceuticals from porousstructure 104.

In some embodiments of the disclosure, the porous structure is made outof a resorbable/degradable polymer such as poly lactic-co-polyglycolic(“PLGA”) copolymers, or any other degradable copolymeric combination,such as polycaprolactone (“PCL”), polygluconate, polylacticacid-polyethylene oxide copolymers, poly(hydroxybutyrate),polyanhydride, poly-phosphoester, poly(amino acids), poly-L-lactide,poly-D-lactide, polyglycolide, poly(alpha-hydroxy acid) and combinationsthereof.

Example Methods of Manufacture

Many of the methods and orientations described herein are designed toprovide a porous structure which exhibits at least some expandablequality. Porous structure 104 is optionally adapted and constructed tostretch as it is being deployed within the lumen being treated. In someexample embodiments of the disclosure, porous structure 104 is providedwith stretchability in order to ease positioning porous structure 104relative to support element 102 or another intervening layer, such as agraft or buffering elements.

In an example embodiment of the disclosure, weaving, braiding and/orknitting results in some or all the elasticity of the porous structurebeing achieved due to the structure of the interlaced and/or crimpedand/or textured fibers (curly, slack). This can be achieved by materialelongation properties securing the porous structure to the stent. Insome example embodiments of the disclosure, a porous structure is madeby combining several interlacing techniques such as knitting over abraided porous structure or braiding over a knitted porous structure. Insome embodiments of the disclosure, multiple layers are combined and/orcreated using these techniques. In some example embodiments of thedisclosure, a warp knitted porous structure with “laid in” yarns isused. In some example embodiments of the disclosure, a porous structureis woven using elastomeric or crimped weft to obtain radial elasticity.

In some example embodiments of the disclosure, the porous structure ismanufactured by combining several techniques such as knitting over abraided porous structure or braiding over a knitted porous structure. Insome example embodiments of the disclosure, a weft knitted porousstructure with “laid in” yarns is used. In some example embodiments ofthe disclosure, a porous structure is woven using elastomeric and/orcrimped weft to obtain radial elasticity. Optionally, porous structureincludes at least one fiber oriented generally parallel to the supportelement's longitudinal axis.

In an example embodiment of the disclosure, a manufactured porousstructure is added as a cover to support element 102. Optionally, porousstructure 104 is used separately from support element 102, which isoptionally not used for stenting. In some example embodiments of thedisclosure, porous structure 104 is manufactured directly onto supportelement 102.

In an example embodiment of the disclosure, porous structure 104 ismanufactured by a knitting technique known to those of ordinary skill inthe knitting art for non-analogous arts, such as clothing manufacturingand textiles. Knitting of porous structure 104 is optionally performedby heads having between 20 and 35 needles. Optionally, the head used hasbetween 30 and 45 needles. Optionally, the head used has between 35 and80 needles. An example of the effect of head size on the porousstructure can be seen in FIG. 14, described above, in which a 22 sizehead and a 35 size head are graphed. In FIG. 14, the needle gauges are40.

In some embodiments of the disclosure, the shape and/or size of the knitis controlled by controlling the tension on the fiber being used forknitting. For example, to create a knit with larger eyes, slack isprovided to the fiber during knitting. Optionally, the fiber iscontrolled during knitting to achieve a circular shaped eye when porousstructure 104 is expanded. In an embodiment of the disclosure,pre-tension on the fiber during knitting is approximately 10-20 grams.In some embodiments of the disclosure, post-tension on the fiber duringknitting is 15-25 grams. The stitch length is between 300 and 400microns, in an example embodiment of the disclosure. In some embodimentsof the disclosure, the knitting machine is run at a relatively slowspeed. For example, the knitting machine is run at 10% of speed capacityusing a Lamb Knitting Machine Corp. System Model WK6 with a specialmodification of speed operation measured by percentage.

In an example embodiment of the disclosure, a fiber or a super-fiberyarn with a specific fineness, or a range of fineness, between 5 and 100microns is used to manufacture a knit porous structure. Optionally, yarnwith a fineness of 10 to 20 microns is used to manufacture a knit porousstructure. Optionally, the yarn is finer than 5 microns. Yarn finenessis often referred to in textile terms by “Tex”. This is the weight ingrams of 1000 meters of the yarn. In an example embodiment of thedisclosure, yarn ranging from 0.3 Tex to 10 Tex is used to manufactureporous structure. In some embodiments of the disclosure, a specific yarnfineness is chosen based on the desired porous structure 104characteristics. For example, a 0.5 Tex yarn using a 22 gauge needlehead will, in some embodiments, produce a porous structure withapproximately 12% coverage area.

An example resulting porous structure using the above components andtechniques, should have 5 to 50 courses per cm. Optionally, 20 to 45courses per cm are manufactured. Optionally, a porous structure with30-35 courses per cm is manufactured. FIG. 5 illustrates a knittedporous structure 104 and support element 102 in a crimped, closedposition. FIG. 6A illustrates a knitted porous structure 104 laid on topof a support element 102 in an open position. FIG. 6B shows exampleknitting in detail.

In another example embodiment of the disclosure, weaving techniques areused to manufacture porous structure 104. Narrow needle looms as well asconventional narrow looms can be configured to produce woven tubularstructures. In weaving, at least two layers of warp yarns are interlacedwith intersecting fill yarns.

By carrying the fill yarn alternately back and forth across two layersof warp yarns, a tubular shape is created. The size and shape of theweave are optionally controlled by determining the warp and/or filldensity, the interlacing pattern and/or frequency, the yarn tensionand/or the yarn dimensions and/or elastic properties. The types ofweaves used for a porous structure are optionally one of “plain”,“basket”, “twill”, “sateen”, “leno” and/or “jacquard”. Optionally, allof the fibers of porous structure are the same. Alternatively, warp andweft fibers of a weave are not constructed of the same materials.Optionally, different materials are used to take advantage of theinherent properties of the different materials, for example one materialmay be elastic and a different material may have a high tensilestrength. Optionally, warp fibers are coated and/or are pharmaceuticaleluting while the weft fibers are not, or vice versa.

In another example embodiment of the disclosure, braiding techniques areused to manufacture porous structure 104, for example as described inKnitting Technology, D. J. Spencer-ed., Woodhead Publishing Limited,Abington Hall, Abington, Cambridge, CB1 6AH, England, the disclosure ofwhich is incorporated herein by express reference thereto. Braidingmachines are optionally used to interlace yarns at a variety ofintersecting angles. In braiding, multiple yarns are fed to aninterlacing zone. Interlacing is optionally achieved by rotation of theyarn spools or by a reciprocating needle bed. The size and shape of thebraid is optionally controlled by the number of yarns, the interlacingpattern and/or angle and/or the yarn dimensions and/or elasticproperties. Optionally, all of the fibers of porous structure are thesame. Optionally, warp and weft fibers of a braid are not constructed ofthe same materials, for example where weft fibers are used to providestrength and warp fibers are used to provide stretchability of thebraid.

In another example embodiment of the disclosure, porous structure 104 ismanufactured by an electrospinning process. Electrospinning is atechnique which utilizes a charged polymer solution (or melt) that isfed through a small opening or nozzle (usually a needle or pipette tip).Because of its charge, the solution is drawn toward a groundedcollecting plate (usually a metal screen, plate, or rotating mandrel),typically 5-30 cm away, as a jet. Optionally, support element 102 isplaced on a delivery catheter which is used as a mandrel. During thejet's travel, the solvent gradually evaporates, and a charged polymerfiber is left to accumulate on the grounded target. The charge on thefibers eventually dissipates into the surrounding environment. Theresulting product is a non-woven fiber porous structure that is composedof tiny fibers with diameters between approximately 40 nanometers and 40microns (e.g. a felt), depending on the size of the fibers input intothe system. If the target is allowed to move with respect to the nozzleposition, such as by rotating and/or moving the mandrel along its longeraxis, specific fiber orientations (parallel alignment or a randomalignment, as examples) can be achieved. In some example embodiments ofthe disclosure, porous structure 104 is spun in a helical coil patternonto the mandrel or support element 102. Optionally, porous structure104 includes a plurality of helical coil patterns, constructed by movingthe mandrel back and forth, such as depicted in FIG. 4. Optionally,porous structure 104 is constructed with fibers oriented substantiallyparallel to central axis 106. Optionally, porous structure 104 isconstructed with fibers oriented substantially perpendicular to centralaxis 106. Optionally, porous structure 104 is constructed with fibersoriented in a combination of any of the orientations described orsuggested herein. The mechanical properties of the porous structure areoptionally altered by varying the fiber diameter and orientationdepending on the requirements for treating a patient. For example, insome embodiments of the disclosure, a laser is used to cut specificaperture sizes and/or to ensure that the apertures traverse from theexterior side of porous structure 104 to the interior side of porousstructure 104. Optionally, solvent is used to modify aperture sizes.

Optionally, portions of catheter are masked in order to preventaccidental coverage of the delivery catheter by porous structure 104.Optionally, support element 102 is coated with an adhesive and/or apharmaceutical agent prior to putting the porous structure 104 on thetop of support element 102. In some example embodiments of thedisclosure, the material used to produce the porous structure 104 isimbued with pharmaceutical agents. Optionally, pharmaceutical agents areembedded in the material coating the porous structure 104. In an exampleembodiment of the disclosure, porous structure 104 includes at least oneinner coating proximal to supporting structure 102 which exhibitsdifferent properties than an external coating proximal to patient'sblood vessel. For example, the inner coating is optionally configured toavoid adhesion to the delivery catheter and/or support structure.Optionally, inner coating is configured to adhere to support element102, but not to delivery catheter.

In some embodiments of the disclosure, porous structure 104 is designedto be less sensitive to foreshortening and elongation forces as porousstructure 104 expands upon deployment. This is in part due to theknitted nature of porous structure 104, in some embodiments. Thisproperty allows porous structure 104 to be secured to support element102 at its ends, rather than in another location, such as the middle asdescribed in U.S. App. No. 2005/0038503 to Greenhalgh et al., thedescription of which is incorporated herein by express referencethereto.

In some example embodiments of the disclosure, a porous structure ismanufactured in an at least partially open, wide diameter, condition. Insome example embodiments of the disclosure, the at least partiallystretched porous structure is reduced to a smaller diameter, byheat-setting, crimping and/or folding, after manufacture.

In an embodiment of the disclosure, the diameter of the at leastpartially stretched porous structure is reduced mechanically.Optionally, a funnel 1304 shown in FIG. 12, is used to reduce thediameter of the knitted porous structure 1302, during the manufacturethe porous structure. A knitted porous structure 1302 is drawn down fromthe knitting zone into a narrowing bore, funnel 1304. This results in afinal porous structure diameter that is controllably smaller than thediameter of the needle bed. FIG. 13, illustrates how a porous structureis manufactured using a stretched rubber tube 1402. In this method, theporous structure 1400 is tightly inserted onto a pre-radially stretchedtube 1402, and then the tube is relaxed, compressing the porousstructure and creating a smaller aperture sized porous structure, thesize of which is controlled by the stretch ratio of the rubber tube.

Referring to FIG. 17, an embodiment is shown in which porous structure104 is folded in “n” substantially folds, the folds used to reduce theoverall diameter of enhanced stent apparatus 100 for easier insertionand navigation through the patient. Optionally, the folds are towardsthe same direction. In an embodiment of the disclosure, a folded porousstructure 104 is at least temporarily secured to support element 102.FIG. 10 shows an alternate folded configuration from a perspective view.

An additional or alternative embodiment to folding includes heat settinga polymer includes porous structure 104 to support structure 102. In anembodiment of the disclosure, heat setting is used when porous structure104 includes at least one polymer material. Determination of heatsetting conditions is related to the polymer's heat transitiontemperatures, in an embodiment of the disclosure. Heat setting isperformed in the temperature range between T_(g) and T_(m) of thepolymer. At this range the polymer becomes amorphous and is shrunk tosupport element 102, establishing an overall enhanced stent apparatus100 radius that is not much more than the support element 102 radius.For example, porous structure 104 adds less than 10 microns in diametertotal to support element 102 which is 1 mm in diameter, in someembodiments of the disclosure. At T_(m) the polymer turns into a viscousliquid which loses its mechanical integrity and will stick to supportelement 102 surface. For example, polyethyleneterephthalate (PET) has aT_(g) of 70° C. and a T_(m) of 265° C., therefore the heat settemperature somewhere within that range, in an embodiment of thedisclosure, is 200° C. Using temperatures higher than T_(m) for heatsetting can cause thermal degradation, which results in polymeric chainscission, unzipping of the polymer and/or producing a large array ofoligomeric material that changes the mechanical properties of porousstructure 104 and/or releases poisonous and/or non-biocompatiblematerials, causing an inflammatory reaction in the patient. Otherexample polymers which can be used in heat setting are below in Table 1(not an exhaustive list):

TABLE-US-00001 TABLE 1 Example polymers and temperatures for heatsetting Material name Material name T_(g) T_(m) set temp. PP  18° C.165° C. 140° C. NYLON 6,6  80° C. 256° C. 210° C. PTFE 150° C. 330° C.300° C. PVA 100° C. 230° C. 190° C. Polyurethanes  70° C. 120° C. 100°C. PLLA  60° C. 175° C. 100° C.

Another additional or alternative embodiment to folding includescrimping using at least a crimped support element 102 in combinationwith porous structure 104. In some embodiments of the disclosure, porousstructure 104 is crimped with support element 102. In an embodiment ofthe disclosure, crimping of porous structure 104 and support element 102is performed when it is desirable to reduce the overall diameter ofenhanced stent apparatus 100. For example, a reduced diameter enhancedstent apparatus 100 allows for easier insertion and navigation of theapparatus to the treatment site. In some embodiments of the disclosure,at least a crimped support element 102 provides an object withrelatively stable mechanical properties for more predictable movementduring insertion and navigation.

Optionally, porous structure 104 is made on a non-crimped supportelement 102. A non-crimped support element 102 can be expanded orsemi-expanded during manufacture. In an example embodiment of thedisclosure, porous structure 104 and support element 102 are crimpedtogether. Optionally, excess porous structure 104 material, which iscreated as a result of reducing the profile of support element 102during crimping, is folded with support element 102, such as shown inFIG. 17. In some example embodiments of the disclosure, porous structure104 is made on a crimped or partially crimped support structure 102.When manufacturing a porous structure for placement on an alreadycrimped support structure, consideration may be given to providing aporous structure which is sufficiently stretchable to expand with theradial expansion of the support structure, when implanted at a treatmentsite within a lumen.

Example Methods for Coating a Fiber

In another example embodiment of the disclosure, a manufacturingtechnique is used to cot a fiber that porous structure 104 includes withat least one polymer layer. For example, a dipping technique, shown inFIG. 18, using a biocompatible, hemocompatible, biostable and/orbiodegradable polymer dissolved in an organic solvent is utilized tocreate a dipping solution 1906 for use in coating the fiber includingporous structure 104. The fiber to be coated is optionally placed in aspool 1902, from which the fiber 1904 is drawn to form porous structure104. Additives such as drugs, biological components, enzymes, growthfactors, and/or any other additive mentioned herein or known in the art,may be incorporated into fiber 1904 during the manufacturing process,for example by placing them in solution 1906 and passing fiber 1904through solution 1906. In an embodiment of the disclosure, at least onelayer is used in order to control the drug/biological additive'srelease. For example, more than one solution tank may be provided forfiber 1904 to pass through during manufacture. Fiber 1904 is optionallymoved into a drying oven 1908 with an operational temperature range from37-70° C. (in some embodiments of the disclosure) depending on the drugused, to dry solution 1906 onto fiber 1904. In an example embodiment ofthe disclosure, fiber 1904 is then used by a knitting system to 1910 tomanufacture porous structure 104. Optionally, knitting system 1910 isthe Lamb Knitting Machine Corp. System Model WK6. Optionally, porousstructure 104 is coated with a polymer layer after it has beenmanufactured.

In some example embodiments of the disclosure, support element 102 andporous structure 104 are coated with an additional substance.Optionally, the additional substance is a polymer. Optionally, theadditional substance is drug eluting. Optionally, the coating ishyaluronic acid. Alternatively or additionally, the coating ishyaluronan. Optionally, a different non-woven technology such as wetand/or dry spinning is used to manufacture porous structure 104. In someembodiments of the disclosure, additional coatings are added to achievedifferent effects, for example timed release of pharmaceutical agentsand/or release of a plurality of agents at different times.

Example Methods for Mounting Porous Structure to Support Element

In some embodiments of the disclosure, porous structure 104 is at leasttemporarily secured to support element 102. Advantages of securingporous structure 104 to support element 102, at least temporarily,include: prevention of unraveling and/or run out of fiber from theporous structure weave, dislodgement and/or slipping of porous structure104 with respect to support element 102 during insertion, deliveryand/or deployment. Optionally, support element 102 and porous structure104 are not secured together using an adhesive and/or other securingmeans despite being in a coaxial and proximate relationship in manyembodiments.

In some example embodiments of the disclosure, where support element 102is optionally coated with a polymer, support element 102 and porousstructure 104 are attached together by curing at the same time thepolymer support element coating and the polymer includes porousstructure, and/or coated porous structure, thus adhering the polymerstogether. Optionally, pressure and/or heat is used to adhere a polymercoated support element 102 to a non-coated or polymer coated porousstructure 104, for example when they are both hot. In some exampleembodiments of the disclosure, porous structure 104 includes twocomponents, an external component and an internal component, relative tosupport element 102. Upon the simultaneous curing of the external andinternal components, the polymers of which both adhere together, therebysecuring porous structure 104 to support element 102, which is locatedbetween the components.

In an example embodiment of the disclosure, porous structure 104 issecured to support element 102 in order to avoid porous structuremigration, but not limit porous structure 104 and/or support element 102expandability.

In some example embodiments of the disclosure, an adhesive is used tobond support element 102 and porous structure 104 together. Optionally,porous structure 104 is glued to support element 102 utilizing anynatural and/or synthetic biocompatible adhesive, such as cyanocrylate,thermo plastic elastomers, silanes, laminin, albumin and/or fibrinogenand/or PEG-PEG adhesive, and/or polyurethane adhesive and/or any othersuitable compatible polymeric material. Optionally, when porousstructure 104 is glued to support element 102, wherein the supportelement 102 is a drug eluting stent, the same polymer as used for theelution of the drug is used for attachment of porous structure 104 tosupport element 102.

In an embodiment of the disclosure, porous structure 104 is attached tosupport element 102 at a plurality of points. Optionally, the pluralityof points defines a pattern, such as a line or zigzag of points.Optionally, porous structure 104 compresses onto support element 102 tomaintain an attachment to support element 102. Optionally, the porousstructure is held in place on support element at least partially byfrictional forces. Optionally, porous structure 104 is sewn and/ormechanically entangled onto support element 102. Optionally, heating,pressure, laser welding, UV curing and/or ultrasound are used astechniques to secure porous structure 104 to support element 102.Optionally, a primer, such as parylene, is used on support element 102prior to adhering porous structure 104 to it in order to enhancecohesion.

In some example embodiments of the disclosure, elastic and/or expandableo- and/or c-rings are used to hold porous structure 104 on supportelement 102. Optionally, c-rings are used to avoid hamperingexpandability of porous structure 104. Optionally, the rings are used toat least temporarily secure and/or apply friction to each end of porousstructure 104 to support element 102. Optionally, the rings are coatedand/or embedded with pharmaceuticals for elution, such as describedherein. Optionally, the rings are constructed of a polymer basedmaterial. In some example embodiments of the disclosure, porousstructure 104 is tied to support element 102, optionally using fibers ofporous structure 104. In an example embodiment of the disclosure, a slipring 2102 is used to secure porous structure 104 to support element 102,as shown in FIGS. 28A and B. Slip ring 2102 is adapted to expand withporous structure 104 and support element 102 when they are expanded upondeployment at a lumen treatment site. Optionally, slip ring 2102 isflexible but is rigid enough to secure porous structure 104 to supportelement 102. In an embodiment of the disclosure, slip ring 2102 iscoiled around enhanced stent apparatus 100 when it is in a reducedprofile configuration such that slip ring 2102 overlaps itself at leastpartially. Upon deployment, shown in FIG. 28B, support element 102 andporous structure 104 are expanded to provide treatment to the lumen. Inan embodiment of the disclosure, slip ring 2102 expands with them whilemaintaining sufficient pressure on porous structure 104 to retain it tosupport element 102. In an embodiment of the disclosure, the overlappingportion of slip ring 2102 is reduced as a result of the overall increasein diameter of the slip ring 2102. Optionally, slip ring 2102 includes abiodegradable and/or bioresorbable material. In some embodiments of thedisclosure, slip ring 2102 is under 25 microns thick. Optionally, slipring 2102 is under 15 microns thick. Optionally, slip ring 2102 is under10 microns thick.

Referring to FIG. 15, an embodiment of the disclosure is shown in whichporous structure 104 is attached to support element 102 using a slidingconnection 1602. In an example embodiment of the disclosure, the slidingconnection is established by attaching at least one loop 1604 of porousstructure 104 to support element 102 in a condition that prevents thetwo from becoming separated, but is loose enough to allow sliding ofporous structure 104 with respect to support element 102. In anembodiment of the disclosure, a loose stitch is used to attach porousstructure 104 to support element 102 in a sliding connection. In anembodiment of the disclosure, expansion of porous structure 104 isassisted by utilizing the sliding nature of the connection 1602. Forexample, porous structure 104 is secured to the outermost strut 1606 ofsupport element 102 at its most outlying position 1608. In an embodimentof the disclosure, on the other side of support element 102 porousstructure 104 is also attached to the outermost strut at its mostoutlying position. When support element 102 and porous structure 104 areexpanded during deployment, porous structure 104 is afforded additionalexpandability, in relation to a pre-expanded configuration, as thesliding connection 1602 moves from the most outlying position 1608 onoutermost strut 1606 to an innermost position 1610. The distance 1612,about 1 mm to 6 mm in an embodiment of the disclosure, from the mostoutlying position 1608 to innermost position 1610 provides additionalexpandability to porous structure 104. Optionally, sliding is preventedby securing porous structure 104 to strut 1606 at innermost position1610 as well as most outlying position 1608. Optionally, sliding isprevented by tightening the connection between the two, for example byproviding a tighter stitch.

In some embodiments of the disclosure, porous structure 104 is tied tosupport element 102 using any one of thumb, square, reef, or doublesurgeon's knots. Optionally, the at least one fiber used to constructporous structure 104 is used to tie porous structure 104 to supportelement 102. FIG. 16 shows an example method for attaching porousstructure 104 to support element 102 using knotting. It can be seen thata knotting fiber 1702 is used to secure porous structure 104 to supportelement 102 at various points along a support element strut 1704.Optionally, knotting fiber 1702 is threaded through a plurality of eyes1706 and over support element strut 1704 wherein a knot 1708 is tied tosecure porous structure 104 to support element 102 at least some of theeyes.

As mentioned above, in some embodiments of the disclosure, securingporous structure 104 to support element 102 is also used to reduce thelikelihood of run outs and/or porous structure unraveling. In anembodiment of the disclosure, run outs and/or porous structureunraveling are to be avoided for at least the reasons of: avoidingporous structure protrusion into the lumen and/or rendering porousstructure ineffective for intended treatment of the lumen. In anembodiment of the disclosure, porous structure 104 is secured to supportelement 102 at the ends of support element 102, at least someintersections where porous structure 104 and support element 102overlap, or both and/or every eye at both ends. Any of the methodologiesof securing described above are optionally used to secure porousstructure 104 to support element 102 to prevent run outs and/orunraveling.

In an example embodiment of the disclosure, porous structure 104 istreated to supply temporary enhanced adhesion to support element 102during implantation.

For example, enhanced stent apparatus 100 is optionally dipped in aliquid which causes porous structure 104 to adhere to support element102. Optionally, this adherence is due to surface tension of the liquid.Optionally, this adherence is due to temporary shrinkage of porousstructure 104, which secures it to support element 102 more tightly. Insome example embodiments of the disclosure, temporary cohesion is usedto prevent porous structure 104 from slipping off of support element 102as a result of frictional stress experienced during navigation of thevasculature during implantation.

General Pharmacological Usage

Alternatively or additionally to the physical prevention of debris fromentering the bloodstream, porous structure 104 optionally containspharmaceuticals designed to treat a variety of ailments. In some exampleembodiments of the disclosure, pharmaceuticals are optionally providedincluding one or more pharmacological agents for encouraging cell and/orliposomal growth and/or other endothelial cell growth factors,anti-proliferative, anti-thrombotic, anti-coagulant and/or anti-plateleteffects, tissue engineering factors, immunomodulators, antioxidants,antisense oligonucleotides, collagen inhibitors, hydrophobicpharmaceuticals, hydrophilic pharmaceuticals and/or endothelial cellseeding substances. Optionally, pharmacological therapy rendered from aporous structure is used to accelerate vein to artery conversion.Specific examples of pharmaceuticals that are optionally used withporous structure 104 include: anti-proliferative agents like sirolimus,zolimus or zotarolimus (ABT-578®), paclitaxel and other taxanes,tacrolimus, everolimus, vincritine, viblastine, HMG-CoA reductaseinhibitors, doxorubicin, colchicine, actinomycin D, mitomycin C,cycloporine, and/or mycophenolic acid, triazolopyrimidine and itsderivatives (i.e. Trapidil®, a coronary vasodilating drug); intrapide,glucocorticoids like dexamethasone, methylprednisolone, and/or gammainterferon; antithrombotics like heparin, heparin-like dextranderivatives, acid citrate dextrose, coumadin, warfarin, streptokinase,anistreplase, tissue plasminogen activator (tPA), urokinase and/orabciximab; antioxidants like probucol; growth factor inhibitors liketranilast and/or angiopeptin; antisense oligonucleotides like c-mycand/or c-myb; collagen inhibitors like halofuginone and/or batimistat;liposomes; gemcitabine (i.e. Gemzar®); steroids and corticosteroids forexample cortisone and prednisone; cortisone, prednisone; sirolimus(Rapamycin®); statin drugs like lovastatin and/or simvastatin (i.e.Zocor®); VEGF; FGF-2; micro carriers containing endothelial cells;genes; DNA; endothelial cell seeds; and/or hydrogels containingendothelial cells.

Typically, stents (i.e. support elements) which provide pharmaceuticaltreatment only have the pharmaceutical embedded on the structure of thestent, in particular on the stent struts. This structure is typicallyminimized in order to provide flexibility and reduce cost, among otherreasons. As a result of a minimized support element structure, thestruts of the structure are usually spaced widely apart. Thus, when thestent is in situ, and pharmaceuticals are released into the patient fromthe stent, the pharmaceutical is only diffused from the widely spacedstruts. This prevents even distribution of the pharmaceutical over theentire length of the stent. In addition, stent struts are typicallylarge in relation to endothelial cells and therefore formation of acovering endothelial cell layer typically takes on the order of days orweeks, rendering pharmaceutical elution into body tissues delayed and/orineffective (due to a number of reasons, including the pharmaceuticalbeing washed away by fluids flowing in the lumen before the endothelialcell layer covers the stent).

In contrast, usage of a pharmaceutical enhanced porous structure, suchas described herein, to cover the stent, including the struts, providesfar more surface area in contact with the inner wall of the patient'sblood vessel, thereby enabling more diffusion to take place. Incomparison to conventional techniques for stent deliveredpharmaceuticals, lower concentrations of pharmaceutical are optionallyused with the present disclosure because of its improvedtherapy-rendering surface area. In an embodiment of the disclosure,improved delivery by the presently described disclosure allows for lowerdoses of pharmaceutical to be used in order to render the same relativeamount of treatment, and reduce the overall dosage needed in order toobtain the same results, thus reducing possible side effects. Forexample, a currently recommended concentration of taxol on a drugeluting stent is around 1 μg/mm² of stent surface. In contrast, aconcentration of 0.5 μg/mm² is optionally used with porous structure104, due to its increased treatment rendering surface area. Optionally,the concentration is less than 0.5 μg/mm². As another example, typicalconcentrations of rapamycin and ‘limus drugs today are around 140μg/mm², however, using the herein described porous structure 104 aconcentration of 80 μg/mm² is optionally used to achieve the sametherapeutic effect. In some example embodiments of the disclosure, aslittle as 10 μg/mm² is optionally, used to achieve the same therapeuticeffect. In some example embodiments of the disclosure, concentrations ofpharmaceutical embedded on porous structure are up to 15 times less thanconventionally used today.

In conventional stents, at the struts, the pharmaceutical may notpropagate far enough and/or without effect into the vascular wall, ormay overdose a particular section of the vascular wall, withoutsufficient propagation laterally to the rest of the inner surface whereit is needed. Having additional surface area more evenly covering thestent surface area, porous structure 104 can deliver drugs in a morelocally homogenous way. Optionally, there is an axial profile change indosage. Since distribution of the drug into the tissue is governed bydiffusion, and since the amount of dosage concentration on the struts islimiting due to over toxicity and side effects, spreading the drug in amore even manner is very helpful for obtaining better pharmacokinetics.

In an example embodiment of the disclosure, pharmaceuticals to beadministered to patient are located in and/or on the fibers of porousstructure 104. Examples of where and how pharmaceuticals are optionallylocated in and/or on the fibers of porous structure 104 and/or elutedinclude:

-   -   1. depositing pharmaceutical in the apertures of porous        structure;    -   2. mixing pharmaceutical particles into fibers of porous        structure at fiber creation;    -   3. applying pharmaceutical topically to the porous structure,        such as by spraying;    -   4. dipping porous structure into a solution containing a        pharmaceutical additive, thereby depositing the additive on        and/or in the fibers of the porous structure;    -   5. encapsulating a pharmaceutical additive on porous structure,        optionally using a thermal process;    -   6. grafting a pharmaceutical additive onto porous structure        using plasma treatment;    -   7. etching a pharmaceutical additive into porous structure, for        example via spattering or coating;    -   8. transferring a pharmaceutical additive to porous structure        using concentration differences between the porous structure and        an additive containing substance, for example by adhering micro        carriers containing to pharmaceutical additive to a porous        structure allowing their migration into the porous structure;    -   9. any method known to those of ordinary skill in the art, such        as shown in U.S. Pat. App. No. 2004/0030377 to Dubson et al.,        U.S. Pat. App No. 2005/0187140 to Hunter et al., U.S. Pat. App.        No. 2004/0236407 to Fierens et al., U.S. Pat. No. 6,902,522, to        Walsh, et al., U.S. Pat. No. 6,669,961 to Kim, et al., U.S. Pat.        No. 6,447,796 to Vook et al., U.S. Pat. No. 6,369,039 to Palasis        et al., U.S. Pat. No. 6,939,374 to Banik, et al., and U.S. Pat.        No. 6,919,100 to Narayanan, the contents of which are        incorporated herein by express reference thereto;    -   10. elution of the drug from a polymer coating the porous        structure fibers;    -   11. elution of the drug from the polymer from which the porous        structure is constructed; and,    -   12. incorporating the drug in a biodegradable polymer.

Optionally, embedding of the pharmaceutical occurs before (e.g. mixingpharmaceutical particles into fibers of porous structure at fibercreation), during (e.g. using the dipping method of FIG. 18) and/orafter (e.g. a spray on pharmaceutical after apparatus is made) themanufacture of enhanced stent apparatus 100. In some example embodimentsof the disclosure, a pharmaceutically embedded porous structure 104 isplaced on top of a pharmaceutically treated support element 102. In someexample embodiments of the disclosure, porous structure 104 is coatedwith at least a polymer. In some example embodiments of the disclosure,a porous structure is provided with a polymer coating which contains apharmaceutical which elutes from the coating.

Pharmaceuticals are optionally embedded into porous structure 104 suchthat they are released into the patient over an approximatepredetermined amount of time. For example, pharmaceuticals areoptionally embedded into porous structure 104 for release over thecourse of a week. Other pharmaceuticals are optionally embedded intoporous structure 104 for release over the course of months. Factorswhich vary according to the release schedule of the pharmaceuticalinclude the type of material used to construct porous structure 104, thetype of pharmaceutical being used, the manner in which porous structure104 is constructed, and/or the amount of coverage of support element 102that porous structure 104 provides.

In some example embodiments of the disclosure, 1 microgram ofpharmaceutical per square centimeter of fiber surface coverage (not thearea of the fiber themselves, but the area of the tissue it treats) areais embedded on the fibers. Optionally, up to 200 micrograms ofpharmaceutical per square centimeter of fiber surface area is embeddedon the fibers. Optionally, a higher or lower concentration ofpharmaceutical is used depending on the therapeutic needs of the patientand depending on the type of drug used.

Large and/or Complicated Stereochemistry Molecule Pharmaceutical Usage

In some example embodiments of the disclosure, usage of porous structure104 for enhanced pharmaceutical delivery allows for effective dispersionand delivery of large molecule and complex stereochemistrypharmaceuticals. Traditionally, large molecule pharmaceuticals are notused with drug eluting stents because they don't diffuse very well, andthe widely spaced struts of traditional stents do not facilitate evenand/or widespread diffusion of the large molecule, as described above.In contrast, use of a device with more extensive coverage of a vascularwall would make treatment using large molecule pharmaceuticals morefeasible. This is optionally accomplished by providing porous structure104 and/or support element 102 with large molecule pharmaceuticals forelution and taking advantage of the increased vascular wall coverage ofporous structure 104, due to the smaller aperture sizes in some exampleembodiments. Alternatively or additionally, due to the overgrowth ofporous structure 104 by cells from the body, large moleculepharmaceuticals are more efficiently delivered to the patient aspharmaceuticals are delivered into tissue, rather than being washed awayin the blood stream, for example. Optionally, pharmaceuticals largerthan 700 Dalton, 1,000 Dalton, 3,000 Dalton or up to 50,000 Dalton aredispersed and delivered evenly into patient's vasculature.

Optionally, liposomes are eluted from at least one porous structure 104and/or support element 102. Optionally, steroids, statins,anticoagulants, gemcitabine (Gemzar®), zolimus or zotarolimus(ABT-578®), sirolimus (e.g. Rapamycin®), taxol/paclitaxel, and/or otherlarge or complex molecule pharmaceuticals are eluted from at least oneporous structure 104 and/or support element 102. Referring to FIG. 3,pharmaceutical agents 406 are shown eluting from enhanced stentapparatus 100 into artery 400 from lumen wall 404. Optionally, agents406 elute from porous structure after at least some growth ofendothelial cells 408 through enhanced stent apparatus 100, for examplethe time determined by experimental endothelial cell growth data. Asdescribed elsewhere herein, porous structure 104 optionally acts to trapdebris 402 between the exterior surface of enhanced stent apparatus 100and lumen wall 404.

Timed Release Pharmaceutical Usage

In an example embodiment of the disclosure, pharmaceuticals are elutedfrom an enhanced stent apparatus into overgrown endothelial tissue andnot merely into the interior surface of the lumen being treated. In anexample embodiment of the disclosure, pharmaceutical release is thusoptimized by ensuring that only a pre-defined amount of drug is lostinto the bloodstream and/or into other non-therapeutic media. In someexample embodiments, including, for example, in conjunction with BBBtreatment as described below, endothelial cell growth can assist withpharmaceutical therapy by providing a transfer medium for thepharmaceutical from an implanted stent to the body area being treated.

In some example embodiments of the disclosure, pharmaceuticals areeluted depending on the extent of endothelial tissue growth. Optionally,pharmacological treatment commences after some endothelial cell growthis exhibited through and/or around the enhanced stent apparatus.Optionally, pharmacological treatment begins upon implantation withoutregard to endothelial cell growth. In some example embodiments of thedisclosure, the enhanced stent apparatus is adapted and constructed totime-release pharmaceuticals in accordance with a predeterminedtreatment schedule. Optionally, the predetermined treatment scheduleaccommodates anticipated and/or actual endothelial cell growth rates byutilizing a coating with a predetermined breakdown rate. Optionally,release of pharmaceuticals is determined by time in situ. For example,if it is estimated that it would take 8 hours for endothelial cellgrowth to completely encapsulate the implanted stent, pharmaceuticalslocated in the porous structure of the stent optionally have apredetermined 8 hour delay prior to release and/or elute at a low rateto prevent inefficient or undesirable (i.e. toxic overdose) use of thepharmaceutical. In an embodiment of the disclosure, it takes only fewhours for the endothelial cells to cover the thin porous structure,therefore the time release delay is adapted to match. This may beachieved by coating porous structure 104 with a “diffusion barrier”layer that to inhibits the diffusion of drug for a predefined period.Optionally this may be achieved by using a controlled degradable matrix.Optionally, pharmaceutical release occurs after only partial growth ofendothelial cells around and/or through porous structure and/or stent.Optionally, pharmaceuticals begin to elute immediately upon insertionand/or implantation into a body lumen. Optionally, it is sufficient forpharmaceutical therapy that porous structure 104 has any biologicalcovering, such as mucus, etc. In some embodiments of the disclosure,delay is determined according to the material that is expected toovergrow porous structure 104.

In an example embodiment of the disclosure, timed release ofpharmaceuticals is accomplished by coating and/or constructing porousstructure 104 and/or support element 102 of multiplebiodegradable/resorbable layers. By using layers which offer differentperformance characteristics (e.g. different pharmaceutical, differentdegradation time, stickiness to the body lumen, surface treatmentmodifications (e.g. treatment to make it non-sticky to the lumen)),enhanced stent apparatus 100 can be tailored to perform a specifictreatment schedule. For example, layer #1 (the external layer) includesa material which degrades in 2 hours, layer #2 (an inner layer) includesa pharmaceutical for elution into the patient and which degrades in 10hours minutes, layer #3 (an inner layer) includes a differentpharmaceutical for elution into the patient which degrades in 6 hours,and so on. Naturally, depending on the therapy desired for the patient,the layers and/or performance characteristics of those layers arechanged to provide the desired treatment. It should be noted that abiodegradable layer can be placed in the outermost position which istimed to the expected endothelial cell growth, as described above. Insuch an embodiment, the degradation of the outermost layer is completedat approximately the same time as the completion of the endothelial celllayer overgrowth of enhanced stent apparatus 100, enabling apharmaceutical to be eluted directly into endothelial tissue from asecond layer of enhanced stent apparatus 100.

In an example embodiment of the disclosure, support element 102 elutespharmaceuticals, but treatment is assisted by porous structure 104 whichencourages endothelial cell growth over support element 102. Optionally,the pharmaceutical located on support element 102 elutes slowly to allowfor endothelial cell growth. In some embodiments of the disclosure, therate of elution depends on the local concentration and the anticipateddiffusion rate of the pharmaceutical through the surrounding bodytissue.

In some embodiment of the disclosure, a first pharmaceutical agent iseluted, which is designed to encourage endothelial cell overgrowth,followed by a second pharmaceutical agent designed to treat a malady ofthe patient.

In some embodiments of the disclosure, at least porous structure 104 isattached to the lumen using an adhesive which is impermeable to thepharmaceutical in porous structure 104. However, timed release isachieved by allowing the endothelial layer to overgrow porous structure104, such that the pharmaceutical will elute into the endothelial layerthat is not proximal to the adhesive. Optionally, the adhesive isbiodegradable and/or bioresorbable and merely delays elution.

Blood Brain Barrier (BBB) Therapy

The BBB is the specialized system of capillary endothelial cells thatprotects the brain from harmful substances in the blood stream, whilesupplying the brain with the required nutrients for proper function.Unlike peripheral capillaries that allow relatively free exchange ofsubstance across/between cells, the BBB strictly limits transport intothe brain through both physical (tight junctions) and metabolic (enzyme)barriers. Thus the BBB is often the rate-limiting factor in determiningpermeation of therapeutic drugs into the brain.

In some example embodiments of the disclosure, a pharmaceutical elutingporous structure is used to enable treatments through the BBB. Asdescribed herein, pharmaceutical therapy is often enhanced byendothelial cell growth through and/or around an implanted drug elutingstent. Use of porous structure 104 in brain arteries, allows theendothelium cells to grow over the porous structure 104, thus embeddingporous structure 104 into the arterial tissue. The end result, after theprevious endothelial cell layer has been absorbed by the body is thatporous structure 104, which contains a brain treating pharmaceutical, ison the other side of the endothelium layer, thus on the other side ofthe BBB, with no significant impediment between porous structure 104 andthe brain tissue. In addition, some example embodiments of porousstructure 104 are suitably sized to be used in the narrow lumens foundin the brain. Example pharmaceuticals suitable for use with porousstructure 104 in treating through the BBB include gemcitabine (Gemzar®),and enzastamin, dopamine and dopamine derivatives, and anti-cancerdrugs. In some embodiments of the disclosure, porous structure 104elutes anti-BBB materials for lowering resistance to transmission ofsubstances through the BBB.

Pharmaceutical Treatment of Small Lumens

Currently, small lumens such as small coronary or brain arteries aretreated only with a balloon type catheter. These treatments are shortterm and do not lend themselves to rendering pharmaceutical treatment tothe lumen, as is sometimes desired. Traditional stenting is not oftenperformed at the very least due to the difficulty of navigating a stentinto the small spaces of these arteries. In an example embodiment of thedisclosure, lumens smaller than 2 mm in diameter are treated withpharmaceuticals using at least a pharmaceutical eluting porous structure104, and optionally a support element. Optionally, the support elementis a stent. Optionally, the support element is a balloon on which porousstructure 104 is placed. In an example embodiment of the disclosure, aballoon-type catheter is used to insert porous structure 104 in a smalllumen. The balloon is expanded to cause porous structure 104 expansionand to instigate contact between porous structure 104 and the lumen wallto be treated. In an embodiment of the disclosure, porous structure 104at least partially adheres to the lumen wall. Optionally, abiocompatible adhesive is used to adhere porous structure 104 to thelumen wall. In several preferred embodiments of the disclosure, porousstructure 104 is self-expandable.

In some embodiments of the disclosure, small lumens are treated longterm, which is not performed currently. For example, by implanting atleast the porous structure of an enhanced stent apparatus 100, treatmentcan last on the order of months (e.g. a month or more). Optionally,treatment can last on the order of weeks (e.g. a week or more).

Example Treatment Methods

In an example embodiment of the disclosure, enhanced stent apparatus 100is used for treating, dilating, drugging and/or supporting body lumens,such as blood vessels. In some example embodiments of the disclosure,enhanced stent apparatus 100 is used for treatment of disorders in thecarotid arteries. In some embodiments of the disclosure, enhanced stentapparatus 100 is used for treatment of disorders in the coronaryarteries. As described above, treatment can be rendered through the BBB.Stent apparatus 100 can be a self-expandable stent or use any otherexpansion method. Generally, the support element 102 and/or porousstructure 104 are self-expandable. Optionally, pharmaceuticals are usedto treat a patient via body lumens, for example, as described herein. Insome embodiments of the disclosure, enhanced stent apparatus 100 is usedfor treatment of aneurisms (described below), for example in the brain.In some embodiments of the disclosure, enhanced stent apparatus 100 isused for preventative treatment of vulnerable plaque.

In operation, enhanced stent apparatus 100 is navigated to the area in abody lumen 400, as shown in FIG. 3, where the enhanced stent apparatus100 is to be emplaced, using techniques known in the art. Optionally,enhanced stent apparatus 100 can be expanded within body lumen 400 usingself-expandable techniques known in the art. Optionally, support element102 and/or porous structure 104 are constructed of a thermo-sensitive,shape memory alloy which, when exposed to a patient's natural bodytemperature, assumes an expanded shape within body lumen 400 at sometime after situation in the appropriate location to render treatment.Alternatively, super-elastic or elastic release is used for placing astent in a treatment area. In some example embodiments of thedisclosure, a balloon is used to pre-dilate body lumen 400 at atreatment area prior to implantation of enhanced stent apparatus 100 atthat area, in an at least a two-step (1. pre-dilate, 2. implantapparatus 100) procedure. Optionally, only porous structure 104 isimplanted and not the whole enhanced stent apparatus 100. In someexample embodiments of the disclosure, a balloon is used to post-dilatebody lumen 400 at a treatment area after implantation of enhanced stentapparatus 100 at that area, in an at least a two-step (1. implantapparatus 100, 2. post-dilate) procedure. This kind of procedure iscommonly used when implant apparatus 100 is a self-expandable stent,such as for carotid applications.

In some example embodiments of the disclosure, the porous structure meshis filled with a material which improves the stiffness of the porousstructure temporarily until it arrives at a treatment site in a lumen.In some embodiments of the disclosure, the material is dissolved bynaturally occurring substances in the body, such as enzymes. Optionally,the dissolving is timed to the anticipated overgrowth of porousstructure 104 by the endothelial cell layer. Optionally the material isfibrogane. Optionally, the material is albumin fibrogane helonic acidlaminin.

Example Treatment of Embolic Showers at Insertion and/or Deployment

It is commonplace in stenting procedures to use an embolic showerprotection device which is situated only during the stenting proceduredownstream from the treatment area, the idea being that the protectiondevice will trap debris which falls from the blood vessel walls duringthe stenting procedure. In an example embodiment of the disclosure,usage of enhanced stent apparatus 100 with porous structure 104 obviatesthe need for an embolic shower protection device. The small aperturesize of porous structure 104 is designed to trap arterial wall plaque402 and other debris of a particular size that becomes dislodged duringand/or after the stenting procedure, between porous structure 104 andthe lumen wall 404. In an example embodiment of the disclosure, debrisgreater than the size of the apertures in diameter is prevented fromentering the bloodstream in this manner.

An additional advantage of using implanted porous structure 104 insteadof a conventional embolic shower protection device is that it remains inplace after the procedure. That is, debris which becomes dislodged atsome time after the stenting is performed still becomes trapped byporous structure 104. This is an improvement over the embolic showerprotection device conventionally used, which is removed at theconclusion of the stenting procedure. Optionally, enhanced stentapparatus 100 is used with an embolic shower protection device asreassurance during the stenting procedure. Optionally, porous structure104 filters a particular type or types of debris while support element102 filters another type or types.

It should be noted further that in an example embodiment of thedisclosure the aperture sizes of the porous structure 104 are designedand constructed to permit the passage of blood therethrough. Thisprevents the “jailing” of branching blood vessels which prevents thepassage of critical blood components, such as red blood cells frompassing into the branching vessel. In an example embodiment of thedisclosure, the aperture size of porous structure 104 is larger than theaverage size of a red blood cell, or about 7 microns, allowingthroughput of red blood cells without the risk of producing significanthemolysis. In some example embodiments of the disclosure, theapproximate aperture diameters are greater than 20 microns. In someexample embodiments of the disclosure, the approximate aperturediameters are smaller than 100 microns thus allowing blood to flowthrough while holding large debris (>100 microns) in place.

Carotid stenting is rarely performed currently, due to the high risk ofdebris becoming dislodged during the stenting procedure. This dislodgeddebris then travels to the brain where it often causes serious injury tothe patient. In order to combat this problem of dislodged debris,enhanced stent apparatus 100, which includes porous structure 104, isused for stenting in the carotid arteries in some example embodiments ofthe disclosure.

Example Treatment of Aneurisms

Referring to FIG. 19A, a typical aneurism volume 2002 is depictedpromulgating from a body lumen 2004. FIG. 19B shows a current method oftreating an aneurism called coil embolization. Coil embolization isparticularly indicated for treatment of cerebral aneurisms. Coilembolization of cerebral aneurisms involves the insertion of a catheterthrough the groin with a small microcatheter navigated to the aneurismitself through the cerebral arteries. A coil 2006 is then deployed intothe aneurism filling it from within and thus disturbing the blood flowin the aneurism volume. This effect that leads to the creation of bloodclot, which is trapped in aneurism volume 2002 and which eventuallyturns into a more solid structure, thus reducing the risk of rupture ofthe aneurism. In some treatments, a stent 2008 is also used in order tokeep coil 2006 from falling out of aneurism volume 2002 and into theblood stream. However, in some cases parts of coil 2006 protrude throughstent 2008 and are therefore exposed to the blood flow within the lumen2004. Additionally, safe insertion of coil 2006 into aneurism volume2002 can be a complicated procedure. Additionally, the blood clotproduced might grow through the stent struts into the blood vessellumen, narrowing it possibly to the point of complete occlusion.

Referring to FIG. 19C, an embodiment of the disclosure is shown in whichporous structure 104 located on enhanced stent apparatus 100 is used totreat an aneurism while preventing coil 2006 from protruding into lumen2004. Optionally, a cerebral aneurism is treated by this method. Porousstructure 104 is adapted to have aperture sizes which are small enoughto prevent coil 2006 from protruding into lumen 2004, in accordance withan embodiment of the disclosure. Optionally, a plurality of porousstructures is used at least slightly out of phase in order to prevent atleast a portion of coil 2006 from protruding into lumen 2004. In someexample embodiments of the disclosure, coil 2006 is covered with aporous structure (separate from porous structure 104), thereby creatingmore surface area for the blood to stick to, enhancing the creation of ablood clot within the aneurism volume 2002. In some embodiments of thedisclosure, porous structure 104 is manufactured using anelectrospinning technique.

In an example embodiment of the disclosure, enhanced stent apparatus 100is used to treat an aneurism without the need for coil 2006. In someembodiments of the disclosure, porous structure 104 is adapted torestrict blood flow into aneurism volume 2002, thus causing the trappedblood in aneurism volume 2002 to clot, which in time will solidify andcreate a solid tissue structure thus reducing the likelihood of aneurismrupture or expansion as a result of increased blood flow thereto. Forexample, the aperture sizes in porous structure 104 may be small orspaced widely apart. Optionally, a plurality of “out of phase” porousstructures are used together to restrict blood flow into aneurism volume2002. Optionally, porous structure 104 has apertures smaller than 20microns Eliminating the need of coil 2006 is advantageous, as it makesthe procedure faster, safer, and simplifies the delivery catheter thatcan be used to perform the procedure.

In some example embodiments of the disclosure, porous structure 104 isshorter than support element 102. A shorter porous structure 104 isoptionally used so that only the aneurism is treated and not a healthyportion of the lumen. Optionally, a shorter porous structure 104 is usedto avoid restricting blood flow to a branching vessel. Optionally,porous structure 104 has small aperture sizes on the aneurism side forrestricting flow therethrough, while the other side has larger aperturesto avoid restricting blood flow to a branching vessel.

In some example embodiments of the disclosure, porous structure 104includes a self-expanding material, such as nitinol, having enoughradial force to hold itself in place within the lumen. Optionally, asupport element 102 is not used at all and porous structure 104 providesthe necessary treatment to the aneurism. Optionally, the radial pressureapplied by porous structure 104 is equivalent to about 1 atmosphere.Optionally, the aperture diameters for aneurism treatments are smallerthan 30 microns.

In some embodiments of the disclosure, porous structure 104 alsoprevents blood clots and/or other embolism-causing debris from enteringthe lumen 2004 from aneurism volume 2002.

Example Treatment of Vulnerable Plaque

Identification of vulnerable plaque areas allows prophylactic treatmentof these areas before they can create problems for the patient. In anembodiment of the disclosure, an enhanced stent apparatus 100 is used topreemptively treat lumen areas expected to trigger problematicconditions for the patient in the future. For example, plaque oftenbuilds up in blood vessels which in some cases breaks off in a clump orpartially tears, causing a thrombosis. The downstream movement of theplaque or thrombosis is a potential cause of a heart attack, stroke orother malady in the patient. In some embodiments of the disclosure, anenhanced stent apparatus, including at least porous structure 104 isimplanted at a potentially problematic location within a lumen,preventing the plaque from rupturing and, thus, from entering thebloodstream. In some embodiments of the disclosure, porous structure 104elutes at least one pharmaceutical used for treating the conditionaffecting the lumen, such as those described herein. In some embodimentsof the disclosure, porous structure 104 is made of nitinol as aself-expandable stent, having enough radial force to hold itself inplace, without the supportive element 102.

Example Method of Implantation

In some example embodiments of the disclosure, porous structure 104 ispositioned on a catheter for implantation in a lumen separately from orwithout support element 102. Treatment with a catheter is optionallyprovided by using the catheter to implant porous structure 104 adaptedand constructed for rendering treatment to a lumen over time.Optionally, pharmaceuticals or other therapeutic agents are embeddedwithin porous structure 104, such as described herein. Positioning, inan example embodiment of the disclosure, entails inserting the catheterat least partially through the interior of porous structure 104 alongcentral axis 106. During delivery of porous structure 104 to a treatmentsite within a lumen, a balance is optionally struck between securingporous structure 104 to the catheter during delivery, but not sosecurely as to prevent implantation of porous structure 104 at thetreatment site and pulling the catheter out while leaving the porousstructure 104 inside the lumen intact. For example, porous structure 104is optionally adhered to catheter at selected points using an adhesivesuch as loctite instant adhesive number 40340, 40840, 46040 or 3411-UVcurable. The adhesive is strong enough to prevent any attached porousstructure 104 from slipping off the catheter during delivery, howeverupon self-expansion or other expansion, the bonds between porousstructure 104 and the catheter are broken, allowing for implantation ofporous structure 104 at a treatment site within a lumen. In someembodiments of the disclosure, delivery lasts for 6 hours or less.Optionally, delivery lasts for 3 hours or less. Optionally, deliverylasts for 1 hour or less.

In some example embodiments of the disclosure, the catheter is treatedwith an anti-sticking agent such as Parylene-c, silicon coating and/orTeflon® (PTFE) coating, to help prevent porous structure 104 fromstaying fastened to catheter after deployment at treatment site.Optionally, a thin film is coated onto the catheter which secures porousstructure 104 to the catheter during the delivery, but dissolves upon anapproximate lapsing of time, allowing porous structure 104 to be removedfrom the catheter. Optionally, the thin film includes albumin fibroganehelonic acid laminin. Optionally, the thin film layer is up to a fewmicrons thick. Alternatively, the thin film layer is 0.1 microns inthickness.

In some example embodiments of the disclosure, the mesh-like structureof porous structure 104 is filled and/or encapsulated with a gel typematerial, such as fibrogane, fibrinogen and/or hyaluronic acid and/orlaminin. The gel material stiffens porous structure 104 for delivery,however, upon extended exposure to intra-lumen conditions, the geldissolves leaving only porous structure 104 after some period of time,for example a few hours or days.

In an embodiment of the disclosure, an adhesive material which issensitive to a certain threshold (e.g. 1 atm. up to 20 atm.) of pressureis placed on porous structure 104 such that when the porous structure104 is present and pressed against the lumen, the porous structure 104adheres to the lumen. In an example embodiment of the disclosure, whenporous structure 104 is coated with the pressure sensitive adhesive itis only coated on the lumen side of porous structure 104. Optionally,porous structure 104 is covered with a selectively adhesive materialwhich has a high affinity for adhering to body tissue, for examplefibrin sealant, biological glue, collagen, hydrogel, hydrocolloid, orcollagen algirate, but limited affinity for adhesion to othersubstances, such as a delivery catheter.

Optionally, porous structure 104 is at least temporarily fastened to theinterior surface of the lumen with the assistance of an adhesive. Insome example embodiments of the disclosure, porous structure 104 is atleast temporarily attached using at least one barb or pin located on anexterior surface of porous structure 104 facing the inside surface ofthe blood vessel. Optionally, the adhesive is applied to the exteriorsurfaces of porous structure 104 prior to insertion into the lumen. Insome example embodiments of the disclosure, once porous structure 104 isplaced at the treatment site within the lumen, a support element 102 isimplanted at the same site interior of porous structure 104 in relationto the interior surface of the lumen, thus sandwiching porous structure104 between support element 102 and the lumen.

In some example embodiments of the disclosure, porous structure 104provides mechanical support to a blood vessel wall. Optionally, porousstructure 104 support is in addition to support rendered by supportelement 102. Alternatively, porous structure support 104 is in lieu ofsupport rendered by support element 102. In some example embodiments ofthe disclosure, support element 102 provides no or minimal support tothe blood vessel wall while supporting porous structure 104. Optionally,porous structure 104 provides pharmacological treatment to blood vesselwhile providing no or minimal support to blood vessel. Optionally,porous structure 104 is implanted along with support element 102,however support element 102 degrades in situ, leaving porous structure104. Optionally, porous structure 104 prevents support structure 102from falling apart in large pieces, permitting release of piece ofsupport structure 102 only when below a certain threshold size, forexample under 20 microns in diameter. Optionally, porous structure 104is implanted along with support element 102, however porous structure104 degrades in situ, leaving support element 102. This lastconfiguration is sometimes indicated when porous structure 104 is madeof a polymer containing a pharmaceutical Eliminating the polymer and thepharmaceutical after period of time has an advantage because it reducesthe likelihood of long term side effects such as thrombosis associatedwith the presence of the polymer and the pharmaceutical.

Stent assemblies, with or without jackets, are used in opening vessellumens in a variety of vascular tissue including, inter alia, stenoticcoronary arteries, stenotic carotid arteries and stenotic organvasculature.

Prior Art Radial Force and Stent Diameter Compromise

As noted above, self-expanding stents generally have a tubular shape cutin a pattern that results in spring-like movement of the stent assemblyin the radial direction. These stents are preloaded into deliverysystems by crimping them to a small diameter, then during the procedurethe stents are deployed and expand to the vessel diameter gradually. Thestent acts as a scaffold based on the stent geometry, and a radial forceexerted on the vessel walls by the stent is regarded as radial force(RF).

FIG. 20 includes a graphic illustration 2050 of the reaction force ofconventional stents through crimping and then deployment (e.g., changein stent diameter). Generally, the line 2052 represents the amount ofequivalent linear force required to crimp the stent to a specificdiameter within a 4-12 face polygonal cavity, while line 2054 representsthe amount of force exerted on the vessel walls by the stent while thestent diameter increases.

Generally, the line 2054 passes through a first zone 2056 and a secondzone 2058 during expansion. The first zone 2056 is the radial forcezone, which delivers high radial force until the minimal determined size(radial expansion) of the stent and any other stent assemblycomponent(s), such as an associated stent jacket. The zone 2056 isdesigned to initiate the expansion of the lesion site or otherwisecontact the portion of the body lumen that is damaged. The zone 2056corresponds to the opening of the stent from 0 to 5 mm with relativelyhigh radial force. The second zone 2058 is the conformability zone, thatachieves diameters up to 11 mm with relatively lower radial force.Generally, conventional stents have higher radial force from 0 to 5 mm,and then a lower radial force from about 6 to 11 mm. Conventional stentshave a very high change in radial force across the zone 2058. Thus, theradial force at 5 mm diameter is much higher than the radial force at9.5 mm. As such, conventional stents do not typically provide a widerange of size (i.e., vessel diameter) coverage, as the stents aredesigned to give scaffold coverage proportional to the diameter of thetarget reference site while avoiding a maximum radial force that coulddamage a vessel wall. For example, when the second zone 2058 includesdiameters between 5.5 mm to 9 mm (e.g., 163% change from initialdiameter), the reduction of radial force is greater than 50% and so highthat if a designed expanded stent diameter is +/−1 to 2 mm compared tothe vessel diameter, an inappropriate radial force is applied to thevessel wall. As such, and to help ensure that an appropriate radialforce is applied to the vessel wall, the physician must choose a size ofstent that is usually within 1-2 mm of the vessel wall. In other words,with conventional stents, the stent has a designed expanded stentdiameter that is acceptable within a very small window of vesseldiameters. In some applications, the portion of the vessel to be stentedhas varying diameters along the length of that portion, with differencesof 5 mm or more. Vessels between different patients have differences of5 mm or more, and/or vessels within one patient may have differences of5 mm or more. Thus, there is a wide array of vessel sizes and varyingvessel diameters to be stented, with different stent sizes expected tobe required for each application. Often, the physician might incorrectlychoose the stent size, leading to a situation where under-sizing oroversizing occurs. Under sizing may result in shifting of the stent ornot achieving full stent apposition, raising the risk of thrombosis ormobilization over the stent edges. Oversizing may result in stressingthe walls and generating re-stenosis or perforation. Oversizing andunder-sizing are thus undesirable and the stent apparatus, methods, andkit described herein avoid these undesirable outcomes and the associatedrisks and costs.

Example Stenting of Various Vessel Diameters Using One Embodiment of theStent Apparatus 100

FIG. 21 includes a graphic illustration 2060 of the reaction force ofone embodiment of the stent apparatus 100 through crimping and thendeployment (e.g., change in stent diameter). The one embodiment of thestent apparatus 100 included an open-cell Nitinol stent with the outerporous structure 104 being woven from a single strand of 20 μm diameterPET. The graphic illustration 2060 includes the lines 2052 and 2054 andthe second zone 2058. FIG. 22 includes a table 2062 detailing thechronic outward force during expansion of the one embodiment of thestent apparatus 100. For the one embodiment of the sent apparatus 100tested, the radial force was determined with a segmented head radialforce test device (Blockwise Engineering LCC, Tempe, Ariz., USA). Theone embodiment of the sent apparatus 100 was released directly into thetest device at a start diameter of 5 mm. The test was conducted at atemperature of 37±2° C. to approximate body temperature. The diameter ofthe test stent assembly device was then increased with a speed of 0.2mm/s up to a diameter of 11 mm (full expansion of the one embodiment ofthe stent apparatus 100) while constantly measuring the radial force,representing the chronic outward force of the one embodiment of the sentapparatus 100. Afterwards the diameter of the test device was decreaseddown to 5 mm while constantly measuring the radial force, representingthe radial resistive force of the one embodiment of the sent apparatus100. All radial force values were normalized by the length of the oneembodiment of the sent apparatus 100. Defining the radial force at thelowest allowed diameter (i.e., 5.5 mm) as 100%, the radial force at themaximum allowed diameter (i.e., 9 mm) was 59% of the maximum radialforce. The radial resistive force during compression was about twice ofthe chronic outward force with a similar progression in the diameterrange tested. In some embodiments, the chronic radial force is theradial force applied to the vessel wall by the stent apparatus 100 overan extended period of time, such as for example over the course of theuseful or design life of the stent apparatus 100.

As can be seen, the diameter of the one embodiment of the sent apparatus100 increased from 5.5 mm at 0.330 N/mm outward force to 9 mm at 0.195N/mm outward force, which is a 163% increase in diameter with only a 41%decrease in outward force. Stated differently and when a second expandeddiameter is less than the first expanded diameter, a ratio between thefirst expanded diameter and the second, different expanded diameter ofthe stent apparatus is less than about 1.65 and greater than about 1with the second radial force being within about 170% of the first radialforce. This large range of diameters with a generally small decrease inoutward force results in expansion of the lesion segment while applyingminimal residual radial force to adjacent healthy segments of thevessel. When used to treat an aneurism, the stent apparatus 100 appliesan acceptable residual radial force to the wall of the lumen for anylumen diameter within a range of lumen diameters, such as for examplethe range between about 5.5 mm to about 9 mm. The relevant sizing foraneurism treatment often depends on the size of the index artery. Thestent apparatus 100 is configured to provide adequate chronic radialforces to all diameters within the range that includes a first expandeddiameter to a second expanded diameter. This avoids permanent trauma tothe stented portions and adjacent portions of the vessel. That is, thestent apparatus 100 opens the lesion to its original diameter or basereference diameter, resists collapse, and provides a safe coverage ofthe target lesion/reference site without overexerting on the luminalwalls. Moreover, the stent apparatus 100 conforms to various vesseldiameters over short distances without causing trauma in any area. Assuch, the stent apparatus 100 is configured to expand to any diameterwithin the range of diameters that includes from about 5.5 mm to about 9mm.

In some embodiments, the stent apparatus 100 is configured for use in avariety of body indications. For example, the stent apparatus 100 isconfigured and sized for body lumens that includes arteries, veins,bronchial lumens, biliary lumens, hepatic lumens, any digestive relatedlumen, Otorhinolaryngology related lumen, etc. Generally, the stentapparatus 100 provides similar radial forces (e.g., less than 50%reduction) at variate final reference normal diameters or base referencediameters. Examples of regions in which the stent apparatus 100 isconfigured for use, associated minimum and maximum reference diameters,associated percent increase of minimum and maximum diameters, andassociated percent decrease of radial force are below in Table 2 (not anexhaustive list):

TABLE 2 Example Regions of Use Percent Increase Percent Decrease ofRadial Min. Max. from Min. Force associated with Min. Diameter DiameterDiameter Ref to Diameter Ref. to Radial Reference Reference Max.Diameter Force associated with Max. Region (mm) (mm) Ref Diameter Ref.Femoral 4 7 175% ≤50% Renal 5 6 120% ≤50% Iliac 7 14 200% ≤50% FistulaAV 5 6 120% ≤50% Bronchial 10 12 120% ≤50% Aorta 20 44 220% ≤50% Biliar10 14 140% ≤50% Veins 14 20 142% ≤50% Common Carotid 5.5 9 163% ≤50%Artery

In an example embodiment, as illustrated in FIG. 23 a method 2070 ofstenting includes estimating body lumen diameter(s) associated with aportion of a body lumen in which the stent apparatus 100 will be placedat step 2072; determining, based on the estimated body lumendiameter(s), target expanded stent diameter(s) of the stent assemblywhich is to be placed in the portion of the vessel at step 2074;selecting the stent apparatus 100 for stenting the portion of the bodylumen at step 2076; and implanting the stent assembly 100 in the portionof the body lumen at step 2078.

At step 2072, body lumen diameter(s) associated with a portion of thebody lumen in which the stent assembly will be placed is estimated.Often, a physician uses imaging techniques to determine the estimatedbody lumen diameter(s) of the portion of the body lumen that needs to bestented. In some embodiments, the portion of the body lumen to bestented has, or ideally should have, a generally consistent vesseldiameter (e.g., within 10% variance in diameter). However, in otherembodiments, the portion of the body lumen has, or should have, a variedbody lumen diameter, which in some cases may be a variation of up to 5mm or about 160% variance in diameter. Thus, in some embodiments,multiple body lumen diameters are estimated during the step 2072. Asillustrated in FIG. 24, multiple body lumen diameters such as 2080 a and2080 b of a portion of a vessel 2082 are estimated at step 2072. In someembodiments, the vessel diameter 2080 a is associated with a firstportion of the body lumen 2082 while the body lumen diameter 2080 b isassociated with a second portion of the body lumen 2082. In someembodiments, a lesion 2084 creates a narrowing of the body lumendiameter. In some embodiments and as noted above, the diameters 2080 aand 2080 b are different while in other embodiments the diameters 2080 aand 2080 b are generally the same. Generally, the diameters 2080 a and2080 b are base reference diameters associated with the area that is tobe stented. This avoids mismeasurement in that some lumen diameters canappear smaller when the lumen is restricted in any way, e.g., due to alesion. In some embodiments, the diameter 2080 a is spaced from thelesion 2084 in a first direction and the diameter 2080 b is spaced fromthe lesion 2084 in a second direction that is opposite the firstdirection.

At step 2074, the target expanded stent diameter(s) of the stentapparatus 100 is determined based on the estimated body lumendiameter(s). Generally, the target expanded stent diameter of the stentapparatus 100 coincides with the unaffected areas of the body lumen.That is, the target expanded stent diameter is the diameter of thevessel at locations adjacent the lesion 2084 or are the diameters 2080 aand 2080 b. In some embodiments, the expanded diameter of the stentassembly is generally consistent. However, in some embodiments and asillustrated in FIG. 24, there are multiple target expanded stentdiameters.

At step 2076, the stent apparatus 100 is selected for stenting theportion of the body lumen 2082. In some embodiments, the stent apparatus100 is selected regardless of whether the target expanded stent diameteris generally consistent or whether there are multiple target expandedstent diameters over a range of expanded diameters. Moreover, the stentapparatus 100 is selected when the target expanded stent diameter is anydiameter within the range of about 5 mm to about 10 mm. In someembodiments, the stent apparatus 100 is selected when the targetexpanded stent diameter is any diameter within the range of about 5.5 mmto about 9 mm.

At the step 2078, the stent apparatus 100 is implanted in the portion ofthe body lumen 2082. As illustrated in FIG. 25, the stent assembly ispositioned within the portion of the body lumen 2082 in a retracted orcrimped state (deployment tools are not illustrated in FIGS. 25 and 26).When positioned within the portion of the vessel 2082, the stentapparatus 100 is allowed to expand. As illustrated in FIG. 26, the stentassembly expands to open the body lumen at the site of the lesion 2084.Moreover, the stent apparatus 100 self-adjusts to the adjacent portionsof the body lumen such that the expanded diameter of the stent apparatus100 is the same as or substantially similar to the estimated body lumendiameters 2080 a and 2080 b. That is, the stent apparatus 100self-adjusts and provides an appropriate radial force to the body lumenportions adjacent the lesion 2084.

While the FIGS. 24-26 illustrate the use of the stent apparatus 100 in abody lumen having varying body lumen diameters, the stent apparatus 100can be used in a body lumen having generally consistent vesseldiameters. For example, the stent apparatus 100 can be used in a bodylumen of a first patient having a generally consistent diameter of about5.5 mm. Moreover, an identical stent apparatus to the stent apparatus100 can be used in a body lumen of a second patient having a generallyconsistent diameter of about 9 mm, i.e., a substantially uniformdiameter. In one embodiment, substantially identical stent assembliesare stent assemblies that are 10% of the other in sizing; at least 90%the same composition; and/or are stent assemblies that have identicaldesigns but have slight variations due to manufacturing variances andtolerances. The radial force applied by the stent apparatus 100 is about0.33 N/mm while the radial force applied to the stent apparatus 100 thatis identical to the stent apparatus 100 is about 0.195 N/mm. As each ofthe radial forces (i.e., 0.33 N/mm and 0.195 N/mm) is an acceptableradial force to apply to body lumen walls, the stent apparatus 100 is aone-size-fits-all stent assembly that is configured to expand to anydiameter from about 5.5 mm to about 9 mm. In some embodiments, thestructure of the stent apparatus 100 allows the stent apparatus 100 toact as either a straight stent or a tapered stent. That is, thestructure of the stent apparatus 100 is not designed for apre-determined tapering of the expanded diameter, but instead adapts tothe diameter of the body lumen upon deployment of the stent apparatus100 even across non-uniform diameter body lumen within the target rangeof about 5.5 mm to about 9 mm.

While a lesion 2084 is illustrated in FIGS. 24-26, the method 2070 isalso applicable for the treatment of aneurisms. In those instances, theportion of the body lumen that is to be stented includes an aneurisminstead of a lesion. The stent assembly of the present disclosure may beused in other indications and applications.

Moreover, while the stent apparatus 100 described above in method 2070is designed for use in a common carotid artery to expand to any diameterfrom about 5.5 mm to about 9 mm, the method 2070 is also applicable foruse in each region detailed above in Table 2. In those instances, andfor example when the stent apparatus 100 is designed and sized for usein an aorta, the stent apparatus 100 is configured to expand to anydiameter from about 20 mm to about 44 mm while having equal to or lessthan about a 50% decrease in chronic radial force between the 20 mmexpanded diameter and the 44 mm expanded diameter.

The stent apparatus 100 and/or the method 2070 reduces or eliminatesrisk of sizing choice errors. That is, errors relating to under sizingor oversizing of stent assemblies are minimized or prevented, as thestent apparatus 100 configured for common carotid artery use isconfigured to expand to the range of diameters that includes 5.5 mm to 9mm and in some cases from 5 mm to 10 mm. Similarly, and as provided inTable 2, when the stent apparatus 100 is configured for use in theaorta, the stent apparatus 100 is configured to expand to any diameterfrom about 20 mm to about 44 mm while having equal to or less than abouta 50% decrease in chronic radial force between the 20 mm expandeddiameter and the 44 mm expanded diameter. Moreover, the stent apparatus100 and/or the method 2070 reduces the number of stent assembliesrequired to be stored on-hand. The stent apparatus 100 and/or the method2070 ensures a known predefined radial force expectancy for alldiameters in the range and results in better adaptation to varyingdiameters over the length of the implantation. As such, the use of astent assembly that is configured specifically for vessels havingvariations in diameters, such as a tapered stent, is no longer required.Instead, the stent apparatus 100 is configured for use in portions ofbody lumens having varied diameters, and for use in a range of vesselsizes having generally consistent diameters. The stent apparatus 100eliminates the compromise of selecting stents for different body lumendiameters based on maximum radial force and desired stent diameter. Asthe stent apparatus 100 self-adjusts, the stent assembly automaticallygains optimal expansion and apposition with minimal residual radialforce that does not exceed a maximum safe radial force that avoids orminimizes damage to a body lumen wall.

In some embodiments and when the outer porous structure 104, being wovenfrom a single strand of 20 μm diameter PET, is placed onto the outsideof the stent, the scaffold coverage increases without the need foradditional metal struts. This interface increases target lesion coverageand allows more flexibility with less metal implanted. The benefit offull coverage with the outer porous structure 104 being woven from asingle strand of 20 μm PET placed over a nitinol stent, allows for asuperior treatment giving coverage across a variety of diameters withinthe same site, rather than oversizing in certain areas, or indeed undersizing in some. In some embodiments, the sent apparatus 100 is composedof or includes a super elastic memory material such as nickel titaniumalloys or super elastic polymers such as for example Memory Ultem® bySABIC of Riyadh, Saudi Arabia, or cobalt chromium stents, or other stentmaterials.

In some embodiments, the method 2070 also includes providing stentinginstructions and providing the stent apparatus 100 in association withthe instructions. In some embodiments, the stenting instructions includeinstructions to: estimate body lumen diameter(s) associated with aportion of a body lumen in which the stent assembly will be placed;determine, based on the estimated body lumen diameter(s), targetexpanded stent diameter(s) of the stent assembly; select the stentassembly for stenting the first portion of the body lumen, wherein thestent assembly is configured to expand from an initial diameter toexpanded diameters within a range of expanded diameters while applying aradial force of about 0.20 N/mm to about 0.33 N/mm; and implant thestent assembly in the portion of the body lumen.

In some embodiments, the instructions and the stent apparatus 100 areprovided in a kit.

In some embodiments, the stent apparatus 100 includes the porousstructure 104 and the support structure 102 as described above. In otherembodiments, the porous structure 104 is omitted and the supportstructure 102 includes or is a single-component cut stent.

Experimental Data Relating to One Embodiment of the Stent Apparatus 100

Thirty (30) consecutive eligible patients were enrolled and treated withone embodiment of the stent apparatus 100 having a free diameter of 10.5mm. All patients had high grade stenosis and/or symptomatic stenosis ofthe internal carotid artery. The modified Rankin Scale of thesymptomatic patients was 1.4±0.7. The key inclusion criteria includedhigh grade of stenosis and/or symptomatic stenosis; clinical symptoms ofcarotid stenosis less ≤1 month prior to intervention; and vesseldiameters between 4.7 and 9.0 mm. The key exclusion criteria includedasymptomatic stenosis <80%; simultaneous acute occlusion of intracranialartery; intracranial bleeding; and previous ipsilateral stentimplantation. The patient and lesion characteristics are listed in table2090 of FIG. 27. The lesions characteristics showed a step-in diameterfrom common carotid artery (CCA) of 8.4±0.6 mm to internal carotidartery (ICA) of 5.8±0.6 mm. Twenty-one (21) arteries were withelongations and six (6) of these had severe tortuosity, while nine (9)arteries were relatively straight. All patients underwent duplexultrasound (DUS) and CT or MRI before intervention. Each of the oneembodiment of the stent apparatus 100 were implanted by a transfemoralapproach using local anesthesia. After placing a long (i.e., 90 cm)support sheath (6F, Destination, Terumo Europe, Leuven, Belgium) in thecommon carotid artery, a distal embolic protection device (FilterWireEZ™ of Boston Scientific, Natick Mass., USA) was used in twelve out ofthirty (12/30) patients. Primary stenting was performed withoutpredilatation in all patients. The one embodiment of the stent apparatus100 was implanted (10×40 mm (n=25) and 10×30 mm (n=5)) in the patients.All patients received 0.5 mg Atropine I.V. (Braun, Germany) andpostdilatation was performed with a 5×30 mm balloon (Sterling™ Monorailof Boston Scientific, Natick Mass., USA) at 10 atm. All the cases weredocumented at baseline, including stenting, postdilation and followingthis, removal of the distal filter with an intracranial digitalsubtraction angiography (DSA) in two projections. In the puncture site aclip-based closure device was used (StarClose SE of Abbott Vascular,Santa Clara, Calif., USA). After intervention, all patients werereferred to the stroke unit and had neurological monitoring. DUS wasrepeated after intervention and after 30 days. In a subgroup, a 30 daydiffusion-weighted magnetic resonance imaging (DW-MRI) was performed.All patients were preloaded the day before the intervention withacetylsalicylic acid (ASA) 500 mg and Clopidogrel 300 mg (Sanofi Aventisof Germany). During the intervention between 5,000 to 10,000 IU heparinwere given depending on the active clotting time (ACT), that had to be250 to 300 s. From the intervention, 75 mg clopidogrel (Sanofi Aventisof Germany)/day was given for a minimum of 6 weeks, and ASA (100 mg/day)permanently. The technical success rate was 100%. No pre-dilatationprior to stent placement was performed in any case. In twelve out ofthirty (12/30) cases a distal filter was used. After retrieving thefilter no debris was observed. There were no cases of relevant spasm,distal embolization or dissection. The median treatment time frompuncture to vessel closure was 37.4±8.7 min. The ACT during interventionwas in median 266.3 sec. There were no cases of death or major adverseevents (MAE). No incidence of minor or major stroke occurredperi-procedural or during the 30 days follow-up period. No patientsdeveloped new neurological symptoms. The modified Rankin Scale was 0. Inthe DUS post-procedural and after 30 days, all stents were patent withnormalized doppler speeds. At 30d, the median peak systolic velocity(PSV) was 75.8±9.1. The external carotid artery was patent in allpatients. DW-MRI was performed in ten out of thirty (10/30) patientsafter 30 days, without detection of new ipsilateral lesions.

The high incidence of postprocedural embolizations with conventionalstents (e.g., ⅔ of CAS major adverse cardiac and cerebrovascular events(MACCE) at 30 days) justified the introduction of the one embodiment ofthe stent apparatus 100, which includes the porous structure 104, tooffer a permanent protection upon the stent implantation as it isdesigned to prevent peri-procedural and late embolization by trappingpotential emboli against the arterial wall, while maintaining perfusionto the external carotid artery and branch vessels.

In some embodiments, the small pore size of the porous layer 104provides neuroprotection with a significant reduction of the incidenceand volume on DW-MRI new lesions at 30 days after CAS vs. conventionalstents historical data.

In terms of clinical performance, a review of 550 patients treated withthe one embodiment of the stent apparatus 100, demonstrated an overallcomplication rate of 1% after 30 days with a near elimination ofpost-procedural events. In a prospective all-referral-study of 101patients treated with the one embodiment of the stent apparatus 100,only one periprocedural minor stroke was found without any other relatedcomplication at one-year follow-up, with a single case of intrastentrestenosis. No complications and no minor or major strokes were observedin thirty patients in the follow-up.

The step differences were in median more than 2 mm. In previousapproaches, tapered stents (TS) implanted in a swine model displayedthat the low radial force reduces intimal hyperplasia leading tosignificantly less restenosis. The TS confirmed a lower rate ofrestenosis in comparison to straight stents in clinical trials, withoutprevention in peri-procedural events. However, and as noted above, theone embodiment of the stent apparatus 100 eliminates and superates theneed for any tapered stent assembly. The one embodiment of the stentapparatus 100 stent demonstrates an extreme adaptability with a nearflat chronic outward force profile in the range of 5.5 to 9.0 mm (i.e.,only about 40% drop force).

In this series of otherwise routine CAS in consecutive patients, the oneembodiment of the stent apparatus 100 demonstrates that it can be safelyimplanted with respect to the vessel architecture, providing a near flatchronic outward force profile in in the range of 5.5 to 9.0 mm.Experimental data relating to the use of the one embodiment of the stentapparatus 100 demonstrate prevention of post-procedural embolic events.

In some embodiments, the stent apparatus 100 expands to a final diameterthat is within a range of final diameters while maintaining a chronicradial force that is within a range of chronic radial forces. In someembodiments, the range of final diameters is from about a first finaldiameter to about a second final diameter that is double the size of thefirst final diameter. In some embodiments, and with the stent apparatus100 sized accordingly, the range of final diameters is from about 10 mmto about 20 mm. However, other diameters are considered here, such asfor example those listed in Table 2. In some embodiments, the range ofchronic radial forces is from about a first chronic radial force toabout a second chronic radial force that is approximately half of thefirst radial force. In some embodiments, the final chronic radial forceis inversely proportional to the final diameter. That is, as the finaldiameter increases, the final chronic radial force decreases. Stateddifferently, the second final diameter is twice the size as the firstfinal diameter and the stent apparatus 100 provides approximately 50%(or at least 50%) of the first chronic radial force when expanded to thesecond final diameter. However, in other embodiments an inverserelationship between the final diameter and the final chronic force isnot required, but the chronic radial force applied by the stentapparatus 100 does not reduce by more than 50% over the range of finaldiameters. In some applications, the range of chronic radial forces isfrom about 0.7 N/mm to about 0.35 N/mm, but can be as low as 0.02 N/mmand 0.1 N/mm.

In some embodiments, and for the stent apparatus 100 used in the method2070, the porous structures 104 described herein can be replaced with apolymer stent jacket or polymeric graft jacket. In some embodiments, theporous structure 104 is omitted.

In some embodiments, the stent apparatus 100 is a dual therapy stent, abioresorbable vascular scaffold, a bio-engineered stent, a drug elutingstent, and/or a bare metal stent.

Prior Art Stent and Jacket Configurations

Referring to FIG. 31a , a stent apparatus 100 includes a stand-alonetubular stent 202, without a jacket, herein bare stent 202. Bare stent202 typically includes a metal or polymer tubular structure havinglarge, mesh-like, apertures 270. Bare stent 202 is shown encircling aballoon 260 and, upon expansion of balloon 260, bare stent 202 expandsradially outward.

As seen in FIG. 31b , bare stent 202 has expanded radially in vessellumen 125 to press against a stenotic area of tissue 240, therebycompressing and cracking stenotic area 240 radially outward. Followingdeployment of stent apparatus 100, vessel lumen 125 expands, allowingbetter circulation through lumen 125.

Deployment of bare stent 202, however, causes damage to a basalaminaintimal layer 127 resulting in the formation of scars 242, plaques 244and new stenotic lesions 240 that protrude through apertures 270. Overthe long-term, a large percentage of the recipients of bare stents 202will develop significant stenotic lesions 240 that block vessel lumen125, causing what is known as restenosis.

To prevent restenosis, (FIG. 31c ), stent assemblies 200 have beendeveloped including stents 202 with an internal or external jacket 204having small apertures. Stent assembly 200 is shown in position around aspindle holder 180, emerging from a compression sheath 182, with stent202 and stent jacket 204 in substantial tubular alignment. Typically,the jacket is formed of a polymer.

During expansion, jacket 204 prevents embolitic debris 121 generatedfrom plaques along basalamina intimal layer 127 from entering vessellumen 125.

In FIG. 31d , stent assembly 200 is expanded radially in vessel lumen125 so that jacket 204 presses stenotic tissue 240 radially outward.Following deployment of the stent assembly 200, stent jacketsubstantially prevents scars 242, plaques 244 and stenotic lesions 240from protruding through apertures 270. In spite of substantiallypreventing restenosis, stent jacket 204 creates its own set of problemsrelated to formation of an embolism 300.

As noted above, to provide sufficient strength, stent jacket 204 may bemade of interlacing knitted fibers, and/or fibers subject to chemical orheat treatments, all of which tend to increase the thickness of fibers210 and bulk of jacket 204, seen in FIG. 32.

Within 48 hours following implantation of stent assembly 200 a layer ofendothelial cells 220 coat stent jacket fibers 210 and basalaminaintimal layer 127, as seen in FIG. 32.

Endothelial cells 220 have a diameter 222 of approximately 20micrometers and maintain adherence to basalamina intimal layer 127 butgenerally do not substantially adhere to jacket fibers 210.

Fibers 210 in stent jacket typically have a thickness 212 of 20micrometers so that endothelial cell 220 that straddles fiber 210, willhave no attachment to basalamina intimal layer 127 and will easilydislodge from fiber 210.

Additionally, fibers 210 are typically spaced a distance 218 of lessthan 20 micrometers so that endothelial cell 220 that straddles betweentwo fibers 210, will attach to the two adjacent fibers 210 and will havea marginal attachment to basalamina intimal layer 127 therebetween;again resulting in a cell 220 that is easily dislodged from fibers 210.

Single endothelial cells 220 that become detached from basalaminaintimal layer 127, are not large enough to be recognized by platelets asforeign bodies around which to aggregate. However, as seen in FIG. 33,during natural movement of fibers 210, for example during regularpulsation of blood in circulation, a release of multiple interconnectedcells 220 occurs.

In this case four endothelial cells 220, have broken loose frombasalamina intimal layer 127, and are freely floating in vessel lumen. Aplatelet 310, having a diameter 320 of between four to ten times thediameter of endothelial cells 220, is attracted to masses that includeat least two endothelia cells 220 and endothelial cells 220 provide anexcellent attractive target for platelet 310.

As seen in FIG. 34, a single platelet 310 has adhered to dislodgedendothelial cells 220. As seen in FIG. 35, as a result of chemotaxis,additional platelets 310 have aggregated around endothelial cells 220 toform an embolism 300.

As noted above, embolism 300, including aggregated platelets 310,presents a health threat that can form at any time followingimplantation of stent jacket 204 causing an estimated 2% of allrecipients of jacketed stents 204 to eventually develop necrosis ofvital organs and/or die.

The tremendous and constant threat of emboli 300 from stent-and-jacketassembly 204 (FIG. 33) has resulted in lifetime administration ofplatelet aggregation reduction APIs. There are many life-threateningsequelae associated with Clopidogrel and there are many clinical trialsbeing conducted on alternative platelet aggregation reducing APIs,including: Ticlopidine, Cangrelor, ARMYDA-2, and Prasugrel.

(Journal of Interventional Cardiology “TCT Annual Meeting: AntiplateletAgents”; Volume 19 Page 193-April 2006.)

As noted above, lifetime administration of platelet aggregation reducingAPIs, herein Clopidogrel, present problems to many sectors of thepopulation.

For example, many jacketed stent recipients develop reactions thatrequire cessation of Clopidogrel, such reactions include: ulcers, skinrashes, and syncope. With high bulk jacketed stents, Cessation ofClopidogrel puts the patient at risk for developing a life threateningembolus 300.

In addition to the hazards of embolus 300, there are patients who, notonly must cease taking Clopidogrel and its accompanying risks, but mayalso develop conditions that are life threatening of themselves,including myelotoxicity, acquired hemophilia and TTP.

Additionally, there are the conditions that the patient may have thatprevent the administration of Clopidogrel, including unresponsiveness toa platelet aggregate reducing API, an antithrombin deficiency,hereditary antithrombin deficiency (HD), immune depression, low CCR5Delta 32 homozygous genotype (CCR5), acquired hemophilia, AIDS, HIV.

Moreover, there are risks presented to virtually every person receivinga jacketed stent. To prevent excessive bleeding in conjunction withvirtually any surgery, Clopidogrel administration must be ceased for asignificant period of time both pre-operatively and post-operatively. Asa result, a patient who has received a stent and is a candidate for anelective surgery, for example prostate removal, is presented with aHobson's choice of ceasing Clopidogrel administration and risking deathfrom emboli, or taking Clopidogrel and risking embolism-free bleeding,hemorrhage and death.

Optimized Stent Assemblies

It has been found that specific configurations of the above-noted stentsand jackets appear to provide advantages as is explained in the“Experimental Data” section. The specific features of theseconfigurations will now be addressed.

Single fiber knits have been used in pantyhose since 1939, and include aplurality of interconnected loops known for strength, elastic qualitiesand thinness. Single fiber knit fabrics would be desirable as low bulkjackets 600 were it not from the problem that any loop along the edge ofthe nylon material can flip 180 degrees and form a run.

FIG. 36 shows a knitted stent jacket 600 including knitted fibers 620forming apertures 110. To prevent flipping in fibers 620, an elastomericbelt 640 has been passed through apertures 110 at the distal end ofstent jacket 600. Optionally, an elastomeric belt 640 is similarlypassed through loops at the proximal end of stent jacket 600 (notshown).

As used herein, any reference to a “knitted material” includes anymaterial that is manufactured by a knitting process, including, interalia: a material knitted from a single fiber, including eithermonofilament or multifilament fiber. The single fiber may include, interalia, polyethylene, polyvinyl chloride, polyurethane, nylon, stainlesssteel, nitinol, or any other metal.

The biostable polymer includes, inter alia, any one of a polyolefin, apolyurethane, a fluorinated polyolefin, a chlorinated polyolefin, apolyamide, an acrylate polymer, an acrylamide polymer, a vinyl polymer,a polyacetal, a polycarbonate, a polyether, an aromatic polyester, apolyether (ether keto), a polysulfone, a silicone rubber, a thermoset,and a polyester (ester imide).

The natural polymer includes, inter alia, a polyolefin, a polyurethane,a Mylar, a silicone, a polyester and a fluorinated polyolefin.

As seen in FIG. 37, knitted stent jacket 104 includes apertures 110 thatare maximized so that fibers 620 provide a small total coverage area inwhich stent jacket 104 covers a stent 102.

In accordance with some embodiments of the present disclosure, in anexpanded state, the area of aperture 110 is between about 50,000 squaremicrometers and about 70,000 square micrometers. In alternativeembodiments, aperture 110 has an area of between about 40,000 squaremicrometers and about 60,000 square micrometers. In other embodiments,aperture 110 has an area of between about 30,000 square micrometers andabout 50,000 square micrometers.

With knitted stent jacket 104 having fibers 620 presenting a small totalcoverage, crimping stent 102 for insertion into compression sheath, 182(FIG. 31c ) for example, is relatively simple.

Additionally, a small total coverage allows crimped stent 102 to have asmall profile, allowing easy maneuverability through lumen 125.

Moreover, with knitted stent jacket 104 having minimal thickness offibers 620, stent jacket 104 substantially has a minimal influence onthe mechanical properties of the stent during the delivery andexpansion.

The location of jacket 104 externally on stent 102 protects basalaminaintimal layer 127 from damage during expansion of stent 102.Additionally, the location of jacket 104 externally on stent 102provides substantial protection against debris 121, seen in FIG. 31d ,entering vessel lumen 125 during expansion of stent 102.

In accordance with some embodiments of the present disclosure, aproximal portion of jacket 104 is attached to a proximal aspect of stent102 using a process selected from the group consisting of: sewing,adhesion, gluing, folding, suturing, riveting and welding. Such anattachment, for example, allows stent 102 to expand with a typicallydifferent coefficient of expansion than that of jacket 104 withoutcausing damage to basalamina intimal layer 127.

As seen in a plan view of knitted stent jacket 600 in FIG. 37, knittedstent jacket 104 includes a small coverage area, for example about 9%,or about 10%, or about 11%, or about 12% of the surface area ofassociated self-expanding stent 102. In general, the coverage area isless than 16%. Hence, in spite of crimping stent 102 prior todeployment, there is no need to fold knitted jacket 104 to fit intosheath 182 (FIG. 31c ) prior to deployment; thereby reducing bulk andincreasing maneuverability of stent assembly 200.

The above-noted parameters of a knitted jacket on a self-expanding stentcan be easily attained in the present disclosure using a fiber diameterof about 12.5 micrometers.

FIG. 38 shows details of knitted jacket 600 in which apertures 110 havea longitudinal length 650 of greater than about 160 micrometers. Inother embodiments, longitudinal length 650 is greater than about 180micrometers. In other embodiments, longitudinal length 650 is greaterthan about 200 micrometers.

In accordance with some embodiments of the present disclosure, apertures110 have a transverse length 642 of greater than about 250 micrometers.In other embodiments, transverse length 642 is greater than about 240micrometers. In other embodiments, transverse length 642 is greater thanabout 230 micrometers.

It will be appreciated that the shorter one of the longitudinal length650 and the transverse length 642 defines the minimum center dimension630 (D) which must be greater than about 230 micrometers, andpreferably, greater than 240 micrometers, and still more preferably,greater than 250 micrometers.

FIG. 39 shows that fibers 620 have a diameter 662, optionally in a rangeof between about 7 micrometers and about 18 micrometers. In otherembodiments, diameter 662 is in a range of between about 10 micrometersand about 15 micrometers. In still other embodiments, diameter 662 is ina range of between about 11 micrometers and about 14 micrometers. Instill other embodiments, diameter 662 is in a range of between about 12micrometers and about 13 micrometers. In still other embodiments,diameter 662 is in a range of between about 12.25 micrometers and about12.75 micrometers. In still other embodiments, diameter 662 of about12.5 micrometers.

Substantially inherent advantages of the measurements of knitted jacket600 become readily apparent in FIG. 40 in which endothelial cells 220are well adhered and stable against basalamina intimal layer 127 due tothe thinness of fibers 620.

As a result of such spacing, a typical endothelial cell 220 will havesubstantial contact with basalamina intimal layer 127 as endothelialcell 220 is prevented from adhering to more than one column of fibers620 due to the distance therebetween.

A group of three endothelial cells 220 is seen adhering to a portion ofknitted stent jacket 600. Endothelial cells 220 have an amoeba-likemovement so that at a fiber junction 692, cell 220 will typically touchdown on junction 692 and move until a substantial portion of cell 220 isin substantial contact with basalamina intimal layer 127. In rare caseswhere a cell 228 fails to properly anchor into basalamina intimal layer127, that specific single cell 228, alone, may have a tendency todislodge due to movement of fibers 620 during normal pulsation in theblood circulation cycle. Due to the stability of adjacent cells 220resulting from substantial contact with basalamina intimal layer 127,multiple cells 220 will not dislodge together with single cell 228.

As shown, single endothelial cell 228 has separated from basalaminaintimal layer 127. However, single cell 228 does not have the necessarymass to be recognized by platelet 310 as a body worthy of adherence. Asa result, there is no formation of the above-noted life-threateningembolism 300 associated with aggregation of platelets 310.

Typically, to ensure stability of endothelial cells 220, a patientreceiving stent jacket 100 will be given a platelet aggregation reducingAPI, for example Clopidogrel, for no more than six months, and possiblyless. For example, the patient may receive Clopidogrel for no more thanfor five months, no more than for four months, no more than for threemonths, no more than for two months, or no more than for one month.

At times, the patient receiving stent jacket 100 will not be given aplatelet aggregation reducing API, the unique property of the fiberdiameter, as illustrated in FIG. 30, and the advantage of the apertureminimum center dimension D, alone or in combination, relieving the needfor the platelet aggregation reducing API, altogether. Thus, if thepatient is scheduled to undergo elective surgery during the six-monthadministration, Clopidogrel may be discontinued without substantial fearof platelet aggregation.

Further, if, during a six-month administration period, the recipient ofstent jacket 600 has any reaction, including ulcers, skin rashes,syncope, myelotoxicity, and TTP, Clopidogrel may be immediately ceasedwithout substantial fear of embolism generation.

Further, Clopidogrel administration may be ceased or not initiated inthe face of patient unresponsiveness to Clopidogrel, an antithrombindeficiency, HD, immune depression, low CCR5, acquired hemophilia, AIDS,and HIV.

Experimental Data

Reference is now made to the chart below showing experimental data,which together with the above description, illustrate the disclosure ina non-limiting fashion.

Optimization of jacket stent fiber thickness and aperture square areareduces the need for an anti-coagulation agent, for example Clopidogrel.

Maintaining small total coverage areas provides several additionaladvantages:

-   -   1. crimping the stent for insertion is relatively simple;    -   2. profile of the crimped stent is small;    -   3. stent jacket substantially has a minimal influence on the        mechanical to properties of the stent during the delivery and        expansion; and    -   4. jacket does not require folding during crimping when the        coverage area of the stent is about 9%, or about 10%, or about        11%, or about 12% in self-expanding stent. In general, the        coverage area is less than 16%.

The chart below provides support that the above-noted parameters ofjacket coverage on a stent can be easily attained in the presentdisclosure using a fiber diameter of about 12.5 micrometers.

TABLE-US-00003 Fiber Head Apertures Size Covered Stent Size size NeedleAper- Transverse Longitudinal area [mm] [μ] No. ture No. [μ] [μ] [%] 2.512.5 22 44 166 291 11% 2.75 12.5 22 44 184 291 10% 3 12.5 22 44 202 29110% 3.5 12.5 22 44 237 291 9% 4 12.5 35 70 167 291 11% 4.5 12.5 35 70189 291 10% 5 12.5 35 70 212 291 9& 5.5 12.5 35 70 234 291 9%

It is understood that the phraseology and terminology employed herein isfor descriptive purpose and should not be regarded as limiting.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the disclosure belongs. In addition, the descriptions,materials, methods, and examples are illustrative only and not intendedto be limiting. Methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of the presentdisclosure.

As used herein, the terms “comprising” and “including”, or grammaticalvariants thereof are to be taken as specifying the stated features,integers, steps or components but do not preclude the addition of one ormore additional features, integers, steps, components or groups thereof.This term encompasses the terms “consisting of” and “consistingessentially of”.

As used herein, “a” or “an” mean “at least one” or “one or more”. Theuse of the phrase “one or more” herein does not alter this intendedmeaning of “a” or “an”.

It is expected that during the life of this patent many relevant stentjacket materials will be developed and the scope of the term stentjacket is intended to include all such new technologies a priori.

As used herein, the term “about” refers to no more than ±10% of a givennumerical value, as applicable.

Additional objects, advantages, and novel features of the presentdisclosure will become apparent to one ordinarily skilled in the artupon examination of the following examples, which are not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present disclosure as delineated hereinabove and as claimed in theclaims section below finds experimental support in the followingexamples.

It is appreciated that certain features of the disclosure, which are,for clarity, described in the context of separate embodiments, may alsobe provided in combination in a single embodiment. Conversely, variousfeatures of the disclosure, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable sub combination.

Although the disclosure has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those of ordinary skill in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present disclosure.

What is claimed is:
 1. A method of using a stent assembly adapted tostent a range of body lumen sizes, which comprises: providing stentinginstructions, which comprise instructions to: estimate body lumendiameter(s) associated with a portion of a body lumen in which the stentassembly will be placed; determine, based on the estimated body lumendiameter(s), target expanded stent diameter(s) of the stent assembly;select the stent assembly for stenting the portion of the body lumenbased on the target expanded stent diameter(s), wherein the stentassembly is configured to expand from an initial diameter to one or moreexpanded diameters within a range of expanded diameters while applying aradial force of about 0.20 N/mm to about 0.33 N/mm; wherein the range ofexpanded diameters is from about 5.5 mm to about 9 mm; and wherein thetarget expanded stent diameter(s) is/are within the range of expandeddiameters; and implant the stent assembly in the portion of the bodylumen; and providing the selected stent assembly in association with thestenting instructions.
 2. The method of claim 1, wherein the stentassembly is configured to expand to all diameters within the range ofexpanded diameters.
 3. The method of claim 1, wherein the portion of thebody lumen in which the stent assembly will be placed comprises alesion; and wherein the estimated body lumen diameter(s) comprise: afirst estimated body lumen diameter that is spaced in a first directionfrom the lesion; and a second estimated body lumen diameter that isspaced in a second direction from the lesion; wherein the firstdirection is opposite the second direction.
 4. The method of claim 1,wherein the instructions further comprise instructions to: when theportion of the body lumen defines varying body lumen diameters, allow afirst portion of the stent assembly to expand to a first expandeddiameter that is within the range of expanded diameters and allow asecond portion of the stent assembly to expand to a second expandeddiameter that is within the range of expanded diameters.
 5. The methodof claim 4, wherein the first expanded diameter is different from thesecond expanded diameter.
 6. The method of claim 1, wherein the stentassembly comprises: a knitted stent jacket, comprising an expansiblemesh structure formed from fibers having a diameter between about 7micrometers and about 40 micrometers; and an expansible stent,operatively associated with the knitted stent jacket; wherein theexpansible mesh structure comprises a retracted state that is associatedwith the initial diameter and a deployed state that is associated withthe one or more expanded diameters, wherein the expansible meshstructure defines apertures having a minimum center dimension greaterthan about 100 micrometers and no more than about 300 micrometers beforeimplantation and when the expansible mesh structure is in the deployedstate, wherein the expansible mesh structure has a thickness of greaterthan about 12.5 micrometers to no more than about 100 micrometers.
 7. Amethod of stenting, which comprises: estimating a base referencediameter(s) associated with a portion of a body lumen in which a stentassembly will be placed; determining, based on the estimated basereference diameter(s), target expanded stent diameter(s) of the stentassembly which is to be placed in the portion of the body lumen;selecting the stent assembly for stenting the portion of the body lumen,wherein the stent assembly is configured to: expand from an initialdiameter to one or more expanded diameters within a range of expandeddiameters; wherein the range of the one or more expanded diameters isfrom about 5.5 mm to about 9 mm; and wherein the target expanded stentdiameter(s) is/are within the range of the one or more expandeddiameters; apply a chronic radial force to a wall that forms the portionof the body lumen in which the stent assembly will be placed, whereinthe chronic radial force is less than about 0.33 N/mm; and implantingthe stent assembly in the portion of the body lumen.
 8. The method ofclaim 7, wherein implanting the stent assembly in the portion of thebody lumen comprises allowing the stent assembly to expand to anexpanded diameter within the range of expanded diameters such that thestent assembly applies the chronic radial force to the wall that formsthe portion of the body lumen in which the stent assembly will beplaced; and wherein the chronic radial force is greater than about 0.20N/mm.
 9. The method of claim 7, wherein the stent assembly is aconfigured to expand to all diameters between about 5.5 mm and about 9mm.
 10. The method of claim 7, wherein, when the portion of the bodylumen defines varying body lumen diameters, implanting the stentassembly in the portion of the body lumen comprises: allowing a firstportion of the stent assembly to expand to a first expanded diameterthat is within the range of the one or more expanded diameters such thatthe first portion of the stent assembly applies the chronic radial forceto the wall that forms the portion of the body lumen in which the stentassembly will be placed; and allowing a second portion of the stentassembly to expand to a second expanded diameter that is within therange of the one or more expanded diameters such that the second portionof the stent assembly applies the chronic radial force to the wall thatforms the portion of the body lumen in which the stent assembly will beplaced; and wherein the chronic radial force is greater than about 0.20N/mm.
 11. The method of claim 10, wherein the first expanded diameter isdifferent from the second expanded diameter.
 12. The method of claim 10,wherein allowing the first portion of the stent assembly to expand tothe first expanded diameter and allowing the second portion of the stentassembly to expand to the second expanded diameter occurssimultaneously.
 13. The method of claim 7, wherein the stent assemblycomprises: a knitted stent jacket, comprising an expansible meshstructure formed from fibers having a diameter of about 7 micrometers toabout 40 micrometers; and an expansible stent, operatively associatedwith the knitted stent jacket: wherein the expansible mesh structurecomprises a retracted state that is associated with the initial diameterand a deployed state that is associated with the expanded diameter(s),wherein the expansible mesh structure defines apertures having a minimumcenter dimension of at least about 100 micrometers to no more than about300 micrometers before implantation and when the expansible meshstructure is in the deployed state, wherein the expansible meshstructure has a thickness of at least about 12.5 micrometers to no morethan about 100 micrometers.
 14. A method of stenting a plurality of bodylumens, which comprises: positioning a first stent assembly in aretracted state within a first body lumen; expanding the first stentassembly to place the first stent assembly in a deployed state withinthe first body lumen; wherein, when the first stent assembly is in thedeployed state, the first stent assembly has a first expanded diameterand applies a first radial force to a first wall that forms the firstbody lumen; positioning a second stent assembly in a retracted statewithin a second body lumen that is different from the first body lumen;and expanding the second stent assembly to place the second stent in adeployed state within the second body lumen; wherein, when the secondstent assembly is in the deployed state, the second stent assembly has asecond expanded diameter and applies a second radial force to a secondwall that forms the second body lumen; wherein the first and secondstent assemblies are at least substantially identical, and the secondexpanded diameter is greater than the first expanded diameter; whereinthe second expanded diameter is between about 220% to about 110% of thefirst expanded diameter; and wherein the second radial force is greaterthan about 50% of the first radial force.
 15. The method of claim 14,wherein expanding the second stent assembly to place the second stentassembly in the deployed state within the second body lumen comprises,when the second body lumen defines varying body lumen diameters:expanding a first portion of the second stent assembly to the secondexpanded diameter that is within a range of expanded diameters; andexpanding a second portion of the second stent assembly to a thirdexpanded diameter that is within the range of expanded diameters; andwherein the range of expanded diameters is from about 9 mm to about 5.5mm.
 16. The method of claim 14, wherein each of the first and secondstent assemblies comprises: a knitted stent jacket, comprising anexpansible mesh structure formed from fibers having a diameter of about7 micrometers to about 40 micrometers; and an expansible stent,operatively associated with the knitted stent jacket: wherein theexpansible mesh structure transitions from the retracted state to thedeployed state, wherein the expansible mesh structure defines apertureshaving a minimum center dimension of at least about 100 micrometers tono more than about 300 micrometers before implantation and when theexpansible mesh structure is in the deployed state, wherein theexpansible mesh structure has a thickness of at least about 12.5micrometers to no more than about 100 micrometers.
 17. A kit comprising:a stent assembly comprising: a knitted stent jacket, comprising anexpansible mesh structure formed from a single fiber having a diameterfrom about 7 micrometers to about 40 micrometers; and an expansiblestent, operatively associated with the knitted stent jacket; wherein theexpansible mesh structure comprises a retracted state and a deployedstate, wherein the expansible mesh structure defines apertures having aminimum center dimension of at least about 160 micrometers in thedeployed state, and wherein the expansible mesh structure has athickness of at least about 12.5 micrometers to no more than about 100micrometers; and instructions for use setting forth a method forexpanding the stent assembly to any expanded diameter in a range fromabout 5.5 mm to about 9 mm while applying a chronic radial force ofabout 0.2 N/m to about 0.33 N/mm.
 18. The kit of claim 17, wherein theinstructions comprise instructions to: estimate body lumen diameter(s)associated with a portion of a body lumen in which the stent assemblywill be placed; determine, based on the estimated body lumendiameter(s), target expanded stent diameter(s) of the stent assembly;select the stent assembly for stenting the portion of the body lumenbased on the target expanded stent diameter(s), wherein the stentassembly is configured to expand from an initial diameter to anyexpanded diameter within the range of expanded diameters while applyinga radial force of about 0.20 N/mm to about 0.33 N/mm; wherein the targetexpanded stent diameter(s) is/are within the range of expandeddiameters; and implant the stent assembly in the portion of the bodylumen.
 19. The kit of claim 17, wherein the stent assembly is aconfigured to expand to all diameters within the range of expandeddiameters.
 20. The kit of claim 17, wherein the instructions furthercomprise instructions to: when the portion of the body lumen definesvarying body lumen diameters, allow a first portion of the stentassembly to expand to a first expanded diameter that is within the rangeof expanded diameters and allow a second portion of the stent assemblyto expand to a second expanded diameter that is within the range ofexpanded diameters.
 21. The kit of claim 20, wherein the first expandeddiameter is different from the second expanded diameter.